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Alessandra Cancellieri

Publications and source records attributed to Alessandra Cancellieri.

18 recordsLinked to original sources
PubMed2006

Migratory marker expression in fibroblast foci of idiopathic pulmonary fibrosis.

BACKGROUND: Fibroblast foci (FF) are considered a relevant morphologic marker of idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), and are recognised as sites where fibrotic responses are initiated and/or perpetuated in this severe disease. Despite their relevance, the cellular and molecular mechanisms responsible for the formation of FF and their role in tissue remodelling are poorly defined. In previous studies we have provided evidence of abnormal activation of the wnt-signaling-pathway in IPF/UIP that is centred on FF and the overlying epithelium. This important morphogenetic pathway is able to trigger epithelial-mesenchymal-transition (EMT), a mechanism involved in developmental and metastatic processes, which is also potentially involved in pulmonary fibrosis. METHODS: Since EMT is characterised by enhancement of migratory potential of cells, we investigated the molecular profile of FF in 30 biopsies of IPF/UIP and a variety of control samples, focussing on the immunohistochemical expression of three molecules involved in cell motility and invasiveness, namely laminin-5-gamma2-chain, fascin, and heat-shock-protein-27. RESULTS: We provide evidence that in UIP these three molecules are abnormally expressed in discrete clusters of bronchiolar basal cells precisely localised in FF. These cellular clusters expressed laminin-5-gamma2-chain and heat-shock-protein-27 at very high levels, forming characteristic three-layered lesions defined as "sandwich-foci" (SW-FF). Upon quantitative analysis SW-FF were present in 28/30 UIP samples, representing more than 50% of recognisable FF in 21/30, but were exceedingly rare in a wide variety of lung pathologies examined as controls. In UIP, SW-FF were often observed in areas of microscopic honeycombing, and were also found at the interface between normal lung tissue and areas of dense scarring. CONCLUSION: These molecular abnormalities strongly suggest that SW-FF represent the leading edge of pulmonary remodelling, where abnormal migration and re-epithelialisation take place, and that abnormal proliferation and migration of bronchiolar basal cells have a major role in the remodelling process characterising IPF/UIP. Further investigations will assess their possible use as reliable markers for better defining the UIP-pattern in difficult cases.

Biomarkers↗
PubMed2006

Clinical experience with gefitinib: an update.

Gefitinib is an orally active, selective epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that blocks signal transduction pathways involved in cell proliferation. This drug demonstrated impressive and durable responses in patients with heavily pretreated non-small cell lung cancer (NSCLC). In two large phase II trials, responses were observed in 9-19% of unselected patients, along with symptom improvement and benefit in quality of life. Biological mechanisms underlying TKI sensitivity have recently been discovered. There is evidence that specific EGFR gene mutations and/or amplification confer a particularly sensitive phenotype, especially in individuals with tumors demonstrating activation of the anti-apoptotic protein Akt. However, in all so far conducted clinical trials, no patient selection has been made, providing a logical explanation for the negative results observed in large phase III studies. In the present review, we will summarize the results observed in clinical trials with gefitinib. We will present results obtained in NSCLC and in other solid tumor, focusing on biological and clinical markers predicting drug sensitivity.

Clinical Trials as Topic↗
PubMed2006

Thoracic endometriosis: current knowledge.

Thoracic endometriosis syndrome includes four well-recognized clinical entities, namely catamenial pneumothorax, catamenial hemothorax, catamenial hemoptysis and lung nodules, as well as some exceptional presentations. The etiological mechanisms of this syndrome are not well understood, and different theories have been proposed. Controversies exist about optimal management, as experience has been drawn from case reports and small clinical series. Surgery, hormonal treatments and combined approaches have all been proposed, with variable results in terms of short and long term outcome.

Diagnosis, Differential↗
PubMed2006

Supracricoid laryngectomies: long-term oncological and functional results.

CONCLUSIONS: Our results confirm that supracricoid laryngectomies (SL) are reliable techniques for glottosupraglottic tumors, even for selected T3 and T4 cases, if the indications are correct. These surgical techniques allow a good quality of life with the preservation of the larynx. OBJECTIVE: SL with cricohyoidoepiglottopexy (CHEP) and cricohyoidopexy (CHP) have been popular over the last 20 years for the treatment of the glottic and/or supraglottic squamous cell carcinoma due to demonstrated good oncological and functional results. We report our experience with these techniques, with special focus on long-term oncological and functional results. PATIENTS AND METHODS: We retrospectively reviewed 206 patients who had undergone SL with CHEP or CHP technique between 1987 and 1998 for glottosupraglottic squamous cell carcinoma in our department. The long-term results for 206 patients with T1-T4 laryngeal carcinomas treated with SL are reported: 90.8% CHEP and 9.2% CHP. The mean follow-up was 62 months. RESULTS: Oncological results: the 5-year actuarial disease-free survival was 85%; the 5-year determinate actuarial survival was 88.3%. Functional results: organ preservation rate was 97%. Phonation was assessed according to the GRBAS scale.

Adult↗
PubMed2004

Akt phosphorylation and gefitinib efficacy in patients with advanced non-small-cell lung cancer.

BACKGROUND: Gefitinib, a specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has activity against approximately 10% of unselected non-small-cell lung cancer (NSCLC) patients. Phosphatidylinositol 3'-kinase (PI3K)/Akt and Ras/Raf/mitogen-activated protein kinase (MAPK), the two main EGFR-signaling pathways, mediate EGFR effects on proliferation and survival. Because activation of these pathways is dependent on the phosphorylation status of the components, we evaluated the association between phosphorylation status of Akt (P-Akt) and MAPK (P-MAPK) and gefitinib activity in patients with advanced NSCLC. METHODS: Consecutive patients (n = 106) with NSCLC who had progressed or relapsed on standard therapy received gefitinib (250 mg/day) until disease progression, unacceptable toxicity, or patient refusal. P-Akt and P-MAPK positivity was determined with immunohistochemistry using tumor tissues obtained before any anticancer treatment. Association of P-Akt and time to progression was determined by univariable and multivariable analyses. All statistical tests were two-sided. RESULTS: Of the 103 evaluable patients, 51 (49.5%) had tumors that were positive for P-Akt, and 23 (22.3%) had tumors that were positive for P-MAPK. P-Akt-positivity status was statistically significantly associated with being female (P<.001), with never-smoking history (P =.004), and with bronchioloalveolar carcinoma histology (P =.034). Compared with patients whose tumors were negative for P-Akt, patients whose tumors were positive for P-Akt had a better response rate (26.1% versus 3.9%; P =.003), disease control rate (60.9% versus 23.5%; P<.001), and time to progression (5.5 versus 2.8 months; P =.004). Response rate, disease control rate, and time to progression did not differ according to P-MAPK status. The multivariable analysis showed that P-Akt positivity was associated with a reduced risk of disease progression (hazard ratio = 0.58, 95% confidence interval = 0.35 to 0.94). CONCLUSIONS: Patients with P-Akt-positive tumors who received gefitinib had a better response rate, disease control rate, and time to progression than patients with P-Akt-negative tumors, suggesting that gefitinib may be most effective in patients with basal Akt activation.

Adult↗
PubMed2004

Bronchoalveolar lavage findings in severe community-acquired pneumonia due to Legionella pneumophila serogroup 1.

BACKGROUND: No specific data are available in the literature on the bronchoalveolar Lavage (BAL) findings of Legionella pneumophila pneumonia. We report on the cytological and immunophenotypical BAL data of three immunocompetent patients with severe community-acquired pneumonia due to L. pneumophila serogroup 1. METHODS: Retrospective chart review. The microbiologial diagnosis was obtained by BAL culture or/and urinary antigen assay. RESULTS: All patients presented with high-grade fever, bilateral chest infiltrates and severe respiratory failure requiring ventilatory support. The cytological BAL pattern at presentation showed in all patients the association of a marked neutrophilia with a variable but remarkable percentage of lymphoblasts. Increased levels of activated T-Lymphocytes (both HLA-DR + and CD25 + cells) and, in 2 out of 3 patients, of T-cells bearing the gamma/delta T-cell receptor were the main immunophenotypical findings on flow cytometric analysis. CONCLUSIONS: We suggest that the association of lymphoblasts with a marked neutrophilia in BAL fluid of patients with a clinical-radiological setting compatible with acute pneumonia should suggest L. pneumophila as a possible etiologic agent.

Aged↗
PubMed2004

Transbronchial needle aspiration improves the diagnostic yield of bronchoscopy in sarcoidosis.

BACKGROUND AND AIM: Transbronchial needle aspiration (TBNA) is a minimally invasive bronchoscopic procedure that allows sampling of hilar and mediastinal lymph nodes in close contact with the airways. We undertook this study to assess the value of TBNA in the diagnosis of sarcoidosis manifesting with intrathoracic lymphadenopathies (stages I and II), and to compare its yield with that of transbronchial lung biopsy (TBLB). METHODS: The results of bronchoscopy with combined TBNA and TBLB in 32 patients with stage I or II sarcoidosis were retrospectively analyzed. RESULTS: Sensitivity was 65.6% for TBNA (stage I, 82.3 %; stage II, 46.6%), and 62.5% for TBLB (stage 1, 52.9%; stage II, 73.3%). The combination of the two methods was associated with the highest diagnostic yield (93.7% overall sensitivity), and allowed significantly better results over both TBNA alone (93.7% vs 65.6%; p = 0.011) and TBLB alone (93.7% vs 62.5%; p = 0.005). CONCLUSIONS: The results of our study suggest that a diagnostic approach combining TBNA and TBLB is safe and effective in the setting of stage I and II sarcoidosis. It also confirmed the value of TBNA, with excellent diagnostic yields especially in stage I of the disease.

Adult↗
PubMed2003

Gefitinib in pretreated non-small-cell lung cancer (NSCLC): analysis of efficacy and correlation with HER2 and epidermal growth factor receptor expression in locally advanced or metastatic NSCLC.

PURPOSE: To evaluate the correlation between HER2 expression and gefitinib (ZD 1839, Iressa; AstraZeneca, London, United Kingdom) efficacy in terms of response rate, time to progression (TTP), and overall survival (OS) time. PATIENTS AND METHODS: Patients with pretreated advanced non-small-cell lung cancer (NSCLC) received gefitinib at a daily dose of 250 mg until disease progression. Tumor tissue specimens obtained at the time of primary diagnosis were collected to determine HER2/epidermal growth factor receptor (EGFR) status by immunohistochemistry. RESULTS: From February 2001 to June 2002, 63 consecutive patients were enrolled onto the study. The overall disease control rate was 58.7% (partial response [PR], 15.9%; stable disease [SD], 42.8%), median TTP was 3.3 months, and median OS was 4.1 months. Among the 43 patients in whom EGFR/HER2 status was determined, we observed six PRs (14%) and 18 SDs (42%). Disease control, including PR and SD, was 40% in the 15 patients overexpressing HER2 and 64.3% in the 28 patients not overexpressing HER2 (P =.126). No difference was found between the two groups in terms of TTP (3.5 v 3.7 months, respectively) and OS (5.7 v 6.8 months, respectively). In addition, we did not find any difference in TTP, OS, toxicity, and symptom outcome in the group of patients overexpressing both HER2 and EGFR compared with patients who had no overexpression of HER2 CONCLUSION: According to these data, efficacy, toxicity, and symptom outcome in patients with NSCLC treated with gefitinib do not seem to be related to HER2 expression.

Adult↗
PubMed2003

Aberrant Wnt/beta-catenin pathway activation in idiopathic pulmonary fibrosis.

To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of beta-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear beta-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (DeltaN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear beta-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the beta-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/beta-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.

Adult↗
PubMed2003

The value of flexible transbronchial needle aspiration in the diagnosis of stage I sarcoidosis.

STUDY OBJECTIVES: Transbronchial lung biopsy (TBLB) during flexible bronchoscopy (FB) is the recommended procedure for diagnosing sarcoidosis in most cases, although its yield in stage I disease is reported to be not as high as when parenchymal involvement is radiologically evident. We undertook this study to assess the diagnostic value of transbronchial needle aspiration (TBNA) in sarcoidosis presenting with hilar and/or mediastinal lymphadenopathy (stage I). DESIGN: Retrospective review of bronchoscopy procedures performed over a 6-year period for the diagnostic workup of hilar and/or mediastinal lymphadenopathy, as detected by chest radiographs. SETTING: Urban academic hospital. PATIENTS: Fifty-five patients with hilar and/or mediastinal lymphadenopathy without pulmonary abnormalities were included in the analysis. INTERVENTIONS: After chest CT and physical examinations, all patients underwent FB with TBNA. Patients thought to have clinicoradiologic findings highly consistent with sarcoidosis, as assessed by the bronchoscopists performing the procedures, underwent combined TBNA and TBLB. RESULTS: A diagnosis of sarcoidosis was established in 32 patients. In the remaining 23 patients, other diseases were pathologically diagnosed. Overall, TBNA was diagnostic in 23 of 32 patients with sarcoidosis (72%) by showing nonnecrotizing granulomas in 28 of 39 lymph node stations sampled (72%). Among the 15 patients who were submitted to both TBNA and TBLB, TBNA exclusively established the diagnosis in 7 of 15 patients (47% increase in the diagnostic rate) and its yield exceeded that of TBLB (11 of 15 patients [73%] vs 6 of 15 patients [40%], respectively). The association of TBNA and TBLB increased the diagnostic yield to 87%. CONCLUSIONS: TBNA may be of great value in the diagnostic evaluation of patients with suspected stage I sarcoidosis, and its use in association with TBLB should be strongly encouraged. TBNA may also preclude the need for further surgical diagnostic procedures in several patients with hilar and/or mediastinal adenopathy due to causes other than sarcoidosis.

Biopsy, Needle↗
PubMed2003

Idiopathic bronchiolitis mimicking diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) is a distinct sinobronchial syndrome which has been almost exclusively reported in East Asia; only a few cases have been observed in non-Asians so far. Since 1990, when one of us described the first European case, we have screened all patients presenting with a clinical, physiopathological and radiological pattern compatible with DPB, in order to assess if the paucity of proven cases in Europe could reflect a lack of awareness of this disease among both pulmonologists and pathologists. Over a 10-years period we identified four additional DPBs, but also interestingly observed five cases of "idiopathic" bronchiolitis (IB) that had both clinical symptoms and high-resolution computed tomography (HRCT) findings indistinguishable from those of DPB, but did not show the typical histological changes. All these patients were Caucasians and presented with dyspnea, productive cough, an obstructive or mixed impairment on pulmonary function tests and chest HRCT features strongly suggesting a grade II to IV DPB. We suggest that diseases classified as IB in this study might be homogeneous entities which are clinically and radiologically similar to DPB.

Adult↗
PubMed2002

Role of fiberscopic transbronchial needle aspiration in the staging of N2 disease due to non-small cell lung cancer.

BACKGROUND: Transbronchoscopic needle aspiration (TBNA) can offer a unique opportunity to identify surgically unresectable lung cancer and to avoid surgical mediastinal exploration in many patients with mediastinal lymph node extension of the tumor. The aim of this study was to assess the yield of TBNA performed with either histology or cytology needles in mediastinal staging of N2 disease due to non-small cell lung cancer (NSCLC). METHODS: Retrospective chart review was carried out on 194 TBNA procedures performed between January 1997 and September 2000 at a single institution. Inclusion criteria were pathologic evidence of NSCLC; contrast enhancement computed tomography scan of the chest suggesting N2 disease; and negative bronchoscopic examination for possible neoplastic lesions at the site of RESULTS: Overall sensitivity and diagnostic accuracy were 71% and 73%, respectively, with no significant differences between 19-gauge and 22-gauge cytology needles. Procedures performed for right paratracheal and subcarinal lymph node stations had a significantly higher yield than those for the left paratracheal station. CONCLUSIONS: TBNA mediastinal staging, performed during the initial diagnostic evaluation of NSCLC, can spare costs and risks of more invasive procedures in patients with inoperable tumors, in patients who are not candidates for operation because of coexistent significant comorbidities, and in patients with N2 disease.

Biopsy, Needle↗
PubMed2002

Abnormal re-epithelialization and lung remodeling in idiopathic pulmonary fibrosis: the role of deltaN-p63.

Products of the p63 gene, a recently described member of the p53 family, are constitutively expressed in the basal cells of human bronchi and bronchioli. The truncated isoforms of the p63 gene (deltaN-p63 proteins) counteract the apoptotic and cell cycle inhibitory functions of p53 after DNA damage, and this property is likely to be central in the cell renewal strategy of stratified epithelial tissues. To investigate the dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we immunohistochemically analyzed the expression of the transactivating and dominant-negative isoforms of the p63 gene on 16 tissue samples obtained from patients suffering from this disorder. In most IPF cases herein investigated, epithelial cells expressing deltaN-p63 were observed at sites of abnormal proliferation at the bronchiolo-alveolar junctions, characterized by epithelial hyperplasia, squamous metaplasia, bronchiolization, and abnormal p53 nuclear accumulation. Similar features were not observed in normal lung and in samples taken from other pulmonary diseases used as controls, including acute interstitial pneumonia, idiopathic bronchiolitis obliterans organizing pneumonia, nonspecific interstitial pneumonia, and desquamative interstitial pneumonia. On the basis of these findings, we can hypothesize a new model for UIP pathogenesis, involving a deregulated development of mesenchymal-epithelial interactions and abnormal proliferation of epithelial cells at the bronchiolo-alveolar junction after cell injury. In our view, the progressive loss of alveolar tissue and lung remodeling after injury in IPF/UIP is concomitantly produced by pneumocyte loss and alveolar collapse on one hand and by progressive bronchiolar proliferation and architectural distortion on the other.

Aged↗