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Claudio Doglioni

Publications and source records attributed to Claudio Doglioni.

32 records · Page 2Linked to original sources
PubMed2005

Optical coherence tomography to detect epithelial lesions of the main pancreatic duct: an Ex Vivo study.

BACKGROUND: Optical coherence tomography (OCT) permits high-resolution, real-time, infrared-generated imaging of tissue microstructures by a probe inserted through the endoscope operative channel. Resolution is approximately 10 microm and the penetration depth of the near-focus probe is about 1 mm. The probe can be inserted into the main pancreatic duct (MPD) through a standard endoscopic retrograde cholangiopancreatography catheter. AIMS AND METHODS: To assess the ability of OCT to identify the structure of the MPD, to distinguish normal and malignant MPD epithelium, and to assess intra- and interobserver reproducibility of OCT images. Multiple sections of neoplastic and non-neoplastic segments of 10 consecutive surgical pancreatic specimens were obtained from patients with pancreatic head adenocarcinoma who had undergone Whipple resection, and repeated OCT radial and longitudinal scanning was done within 1 h of resection and before pathological examination. We compared 249 good-quality images with 100 histopathological sections. RESULTS: OCT recognized a definite, different pattern in 82.9% of tumor-free and in 97.6% of tumor-involved specimens; sensitivity and specificity for discrimination between adenocarcinoma and normal tissue were 78.6% and 88.9%, respectively. Inflammatory and dysplastic changes of the MPD showed an OCT pattern similar to that of the normal tissue in 53.3% of images. Overall, intraobserver reproducibility ranged from 85.1% to 100% and interobserver reproducibility ranged from 69.9% to 100% and from 89.7% to 100% for tumor-free and tumor-involved segments, respectively. CONCLUSIONS: OCT identified the neoplastic and non-neoplastic MPD layer structure and appeared to be a reproducible technique. In non-neoplastic conditions, OCT appeared unable to differentiate between normal and abnormal tissues in about half of the cases.

Adenocarcinoma↗
PubMed2005

Rituximab in patients with mucosal-associated lymphoid tissue-type lymphoma of the ocular adnexa.

Eight patients with ocular adnexal mucosal-associated lymphpid tissue (MALT) lymphoma were treated with rituximab, at diagnosis (n=5) or relapse (n=3). All untreated patients achieved lymphoma regression, while relapsing patients had no benefit. Four responding patients experienced early relapse. The median time to progression was 5 months. The efficacy of rituximab in ocular adnexal lymphoma is lower than that reported for gastric MALT lymphomas.

Adult↗
PubMed2004

Atypical lipomatous tumor: molecular characterization.

PURPOSE OF REVIEW: Atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDLs) are one of the more frequent mesenchymal neoplasms and are characterized by specific chromosome aberrations: supernumerary chromosome or giant marker chromosome or both. Extra copies of known oncogenes such as MDM2, CDK4, SAS, HMGA2 and others are present in this abnormal genetic material. RECENT FINDINGS: In the past few years, several papers have further dissected the genetic alterations present in these tumors, allowing the identification of new potential oncogenes. SUMMARY: ALT/WDLs represent therefore an interesting model for assessing the potential role of these oncogenes, not only in the pathogenesis, but also as a therapeutic target.

Biomarkers, Tumor↗
PubMed2004

CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors.

CDX-2 is a homeobox gene product essential for intestinal development and differentiation. It can be used as a specific marker of colorectal adenocarcinomas and other tumors with intestinal differentiation, but little is known about its expression in endocrine and neuroendocrine (NE) cells and NE primary and metastatic tumors. Using the Cdx-2-88 monoclonal antibody, we evaluated CDX-2 expression in routine samples of 20 normal endocrine/NE tissues and of 299 samples of well-differentiated NE tumors (WDNET) and high-grade NE carcinomas (NEC) from different sites. For 17 cases, we examined primary and corresponding metastatic lesions. We also examined 8 cytologic samples of liver metastases derived from 4 ileal WDNETs, 1 lung WDNET, and 3 pancreatic endocrine tumors. CDX-2 mRNA expression with RT-PCR technique on frozen material was evaluated in 5 WDNETs. CDX-2 was expressed in normal NE cells of the intestine and gastric fundus. High CDX-2 expression was seen in all ileal and appendiceal WDNET, while low levels were seen in WDNETs from stomach, duodenum, and rectum; no reactivity was seen in other WDNETs. Low levels of CDX-2 expression were seen in one third of nonfunctioning pancreatic WDNET where it was more frequently observed in cases with metastatic disease (P = 0.002). CDX-2 was identified in all cytologic specimens of metastatic ileal WDNETs. CDX-2 mRNA analysis confirmed immunohistochemical results. CDX-2 was expressed at high levels in 81% of intestinal NEC. Unexpectedly, variable levels of expression of CDX-2 were seen also in 39% of NEC of other sites, without any relation with the site of origin. This reactivity frequently overlapped TTF-1 expression, suggesting deregulated expression of homeobox genes in NEC. The restricted pattern of CDX-2 expression may have diagnostic value in the identification of the primary site of a metastatic WDNET. Conversely, a limited diagnostic role is suggested for CDX-2 in NEC because of its frequent expression in nongastrointestinal tumors.

CDX2 Transcription Factor↗
PubMed2003

High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis.

BACKGROUND: Syndecan-1 is a transmembrane heparan sulphate proteoglycan that is involved in cell-cell adhesion, organization of cell-matrix adhesion, and regulation of growth factor signaling. METHODS: Specimens from 254 consecutive breast carcinoma (BC) cases (110 N0, 144 N1/2) with long-term follow-up (median, 95 months) were immunostained for syndecan-1, estrogen receptor (ER), progesterone receptor (PgR), and p53; in 154 cases, c-erbB-2 status was known. Syndecan-1 mRNA and protein expression also were evaluated in 20 breast tissue samples (10 normal and tumor pairs). RESULTS: Syndecan-1 was expressed at high levels in 106 (42%) BCs; syndecan-1 up-regulation was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) studies. High syndecan-1 expression was associated with high histologic grade, large tumor size, high mitotic count, c-erbB-2 overexpression, and ER and PgR negative status. At univariate survival analysis syndecan overexpression was related to poor prognosis (P < 0.01 for both overall survival (OS) and disease-free survival). Bivariate survival analysis showed an additive adverse effect for syndecan-1 and c-erbB-2 overexpression. At multivariate analysis, syndecan-1 overexpression was independently associated with poor OS (hazard ratio [HR], 1.71; 95% confidence interval [CI], 1.08-2.69). High syndecan-1 expression also was of independent prognostic value for OS in the group of 102 ER-negative patients (HR, 2.42; 95% CI, 1.21-4.82). Stratifying patients on the basis of the type of adjuvant therapy given, high syndecan-1 expression was associated with a higher risk of death only in patients treated with the cyclophosphamide-methotrexate-fluorouracil regimen (HR, 1.9; P = 0.09); at multivariate analysis for OS, this association proved to be of independent statistical significance (P = 0.03; HR, 2.15). CONCLUSIONS: Syndecan-1 is expressed at high levels in a significant percentage of breast carcinomas and is related to an aggressive phenotype and poor clinical behavior.

Adenocarcinoma↗
PubMed2003

Constitutive expression of DeltaN-p63alpha isoform in human thymus and thymic epithelial tumours.

p63, a member of the p53 family, is involved in the survival and differentiation of reserve/stem cells in different epithelia. To unveil the possible role of p63 in thymic physiology and pathology, we investigated the expression of p63 isoforms in normal thymus, thymomas and other mediastinal tumours. All samples were analysed using immunohistochemistry with three different antibodies: 4A4 antibody recognising all p63 isoforms, p40 antibody reacting only with truncated dominant-negative isoforms (DeltaN-p63) and H-129 antibody recognising all alpha-isoforms. Reverse-transcription polymerase chain reaction (RT-PCR), and real-time PCR analyses were performed on RNA extracted from frozen samples of four thymomas and two primary-mediastinal large-B-cell lymphoma (PMLBCL). In normal thymus, DeltaN-p63alpha was expressed in all cortical and medullary epithelial cells, with decreasing intensity in Hassall's corpuscles. This phenotype was conserved in neoplastic transformation since all 54 investigated thymomas (World Health Organization types A, AB, B1, B2, B3, C) expressed DeltaN-p63alpha (virtually 100% cells). The predominance of DeltaN-p63alpha isoform mRNA was confirmed by real-time PCR. Among other mediastinal tumours, DeltaN-p63alpha was only expressed in those displaying either a stratified epithelial component (teratomas) or epidermoid differentiation (lung carcinoma). Among lymphomas, T-cell-precursor lymphomas did not express p63, whereas most PMLBCL expressed TA-p63alpha (7/8).

Cell Nucleus↗
PubMed2003

Alterations of beta-catenin pathway in non-melanoma skin tumors: loss of alpha-ABC nuclear reactivity correlates with the presence of beta-catenin gene mutation.

To determine the role of beta-catenin pathway in human skin carcinogenesis, 135 non-melanoma skin tumors were analyzed for beta-catenin expression and gene mutations. Intense nucleo-cytoplasmic immunoreactivity for C terminus beta-catenin antibodies was observed in all pilomatricomas and in single cases of trichoepithelioma and squamous cell carcinoma showing peculiar signs of matrical differentiation. Moderate increase of beta-catenin nuclear staining was detected in a significant proportion of basal cell carcinomas, Bowen disease, spiroadenomas, and occasionally also in squamous cell carcinomas, but in these neoplasms only a limited fraction of tumor cells accumulated beta-catenin. Molecular analysis revealed that beta-catenin gene mutations are a peculiar feature of skin tumors with matrical differentiation and correlate with a pattern of intense and diffuse beta-catenin nuclear expression. In contrast, adenomatous polyposis coli (APC) and AXIN2 mutations were not involved in skin tumorigenesis. Analysis of Wnt pathway revealed that TCF-1 and MITF-M were selectively induced in the tumor types harboring beta-catenin mutations, indicating that a Wnt/beta-catenin pathway involving TCF-1 and MITF-M is activated in these tumors. Interestingly, high expression levels of TCF-3 were found in basal cell carcinomas and spiroadenomas. TCF-3 is reported to act as a negative modulator of beta-catenin degradation pathway. Thus, the moderate increase of beta-catenin nuclear staining detected in these tumor types might, at least in part, be due to a TCF-3-dependent mechanism. Finally, we found that the presence of beta-catenin mutations significantly correlated with loss of nuclear immunoreactivity for an antibody raised against the N terminus of beta-catenin (alphaABC). Thus, a combined analysis with C terminus-beta-catenin antibodies and alphaABC Ab may represent a powerful investigative approach for the detection of beta-catenin structural alterations.

Antibodies, Monoclonal↗
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↗
PubMed2002

Transformation of normal human cells in the absence of telomerase activation.

Our knowledge of the transformation process has emerged largely from studies of primary rodent cells and animal models. However, numerous attempts to transform human cells using oncogene combinations that are effective in rodents have proven unsuccessful. These findings strongly argue for the study of homologous experimental systems. Here we report that the combined expression of adenovirus E1A, Ha-RasV12, and MDM2 is sufficient to convert a normal human cell into a cancer cell. Notably, transformation did not require telomerase activation. Therefore, we provide evidence that activation of telomere maintenance strategies is not an obligate characteristic of tumorigenic human cells.

Animals↗
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↗
PubMed2002

[p-ANCA and ASCA antibodies in the differential diagnosis between ulcerative rectocolitis and Crohn's disease].

UNLABELLED: Anti-Saccaromyces cerevisiae antibodies (ASCA) seem to be associated with Crohn's disease (CD), while anti-neutrophil cytoplasm antibodies (p-ANCA) seem to be a recognised marker for ulcerative colitis (UC). AIM: Of our study was to determine whether the presence of ASCA and p-ANCA antibodies could differentiate CD from UC and IBD from aspecific chronic colitis (ACC). METHODS: Serum samples were obtained from 23 patients with CD and 32 with UC, and from 13 patients with aspecific chronic colitis. Diagnosis was established on clinical findings, endoscopy and histology. Determination of ASCA and p-ANCA antibodies was performed using indirect immunofluorescence technique and ELISA, respectively. RESULTS: 20% CD patients against 50% UC patients expressed p-ANCA (p < 0.05). Vice versa 61% CD patients against 16% UC patients expressed ASCA (p < 0.05). The combination of positive ASCA and negative p-ANCA determined a sensibility, specificity and positive predictive value of 45%, 91% and 75% respectively, for diagnosis of CD. The combination of positive p-ANCA and negative ASCA determined a sensibility, specificity and positive predictive value of 44%, 95% and 94% respectively, for diagnosis of UC. CONCLUSION: Our results indicate that ASCA are principally expressed in patients with CD, by contrast p-ANCA seem to be strongly associated with UC. The combination of these two tests can be useful in evaluating patients with indeterminate colitis, distinguishing UC from CD.

Adult↗
PubMedDate not supplied

Identification of calretinin and the alternatively spliced form calretinin-22k in primary pleural mesotheliomas and in their metastases.

BACKGROUND: Antibodies against calretinin represent an established, powerful and reliable immunohistochemical marker in the differential diagnosis between mesothelioma and adenocarcinomas. However, in studies published so far, the exact molecular identity of the immunoreactive protein(s) detected in mesothelioma sections has not yet been determined. MATERIALS AND METHODS: Tissue biopsies from ten mesothelioma samples, primary and metastatic, were analyzed by Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR), in addition to immunohistochemical staining. RESULTS: Besides the selective positive immunoreaction in all 10 samples, calretinin was identified by Western blot analysis and by identification of its mRNA by RT-PCR. In addition, we identified the alternatively spliced form calretinin-22k and the corresponding mRNA, previously detected only in neoplastic cells in colon carcinomas and derived cell lines. CONCLUSION: Our findings demonstrate that the immunoreactivity observed in the mesotheliomas and their metastases investigated in this report is due to the concomitant presence of calretinin and the alternatively spliced form calretinin-22k.

Adult↗