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Alessandro Cama Fabio Verginelli Lavinia Vittoria Lotti Francesco Napolitano Annalisa Morgano Andria D’Orazio Michele Vacca Silvia Perconti Felice Pepe Federico Romani Francesca Vitullo Filippo di Lella Rosa Visone Massimo Mannelli Hartmut P. H. Neumann Giancarlo Raiconi Carlo Paties Antonio Moschetta Roberto Tagliaferri Angelo Veronese Mario Sanna Renato Mariani-Costantini 《Acta neuropathologica》2013,126(4):575-594
Head and neck paragangliomas, rare neoplasms of the paraganglia composed of nests of neurosecretory and glial cells embedded in vascular stroma, provide a remarkable example of organoid tumor architecture. To identify genes and pathways commonly deregulated in head and neck paraganglioma, we integrated high-density genome-wide copy number variation (CNV) analysis with microRNA and immunomorphological studies. Gene-centric CNV analysis of 24 cases identified a list of 104 genes most significantly targeted by tumor-associated alterations. The “NOTCH signaling pathway” was the most significantly enriched term in the list (P = 0.002 after Bonferroni or Benjamini correction). Expression of the relevant NOTCH pathway proteins in sustentacular (glial), chief (neuroendocrine) and endothelial cells was confirmed by immunohistochemistry in 47 head and neck paraganglioma cases. There were no relationships between level and pattern of NOTCH1/JAG2 protein expression and germline mutation status in the SDH genes, implicated in paraganglioma predisposition, or the presence/absence of immunostaining for SDHB, a surrogate marker of SDH mutations. Interestingly, NOTCH upregulation was observed also in cases with no evidence of CNVs at NOTCH signaling genes, suggesting altered epigenetic modulation of this pathway. To address this issue we performed microarray-based microRNA expression analyses. Notably 5 microRNAs (miR-200a,b,c and miR-34b,c), including those most downregulated in the tumors, correlated to NOTCH signaling and directly targeted NOTCH1 in in vitro experiments using SH-SY5Y neuroblastoma cells. Furthermore, lentiviral transduction of miR-200s and miR-34s in patient-derived primary tympano-jugular paraganglioma cell cultures was associated with NOTCH1 downregulation and increased levels of markers of cell toxicity and cell death. Taken together, our results provide an integrated view of common molecular alterations associated with head and neck paraganglioma and reveal an essential role of NOTCH pathway deregulation in this tumor type. 相似文献
23.
Srinivas Vure Karl Pang Lavinia Hallam M. Lui David Croaker 《Pediatric surgery international》2009,25(9):811-813
Congenital midline cervical cleft (CMCC) is an uncommon malformation. We report a case of a baby girl aged 3 days with a CMCC
associated with a cyst reported as a bronchogenic cyst (BC). The pathology is not specific. The association of BC and CMCC
is extremely rare and only five cases have been found in the literature. We report our case and review the relevant literature. 相似文献
24.
Monica Pentenero Walter Giaretti Roberto Navone Isabella Rostan Lavinia Gassino Roberto Broccoletti Paolo Giacomo Arduino Davide Malacarne Sergio Gandolfo 《Journal of oral pathology & medicine》2011,40(3):214-217
J Oral Pathol Med (2011) 40 : 214–217 Purpose: To test the hypothesis that cigarette smokers develop oral potentially malignant disorders or carcinomas in preferential anatomical subsites. Methods: The association of smoking habit with the presence of oral lesions in specific anatomical subsites was assessed in 123 patients using the odds ratio analysis. Results: When compared to all the other subsites, the relative frequency of smokers with lesions was higher in the buccal mucosa and in the floor of the mouth (FOM) (P = 0.002 and P = 0.005), while it was lower in the tongue (P < 0.0005). Smokers were about 7 years younger than non‐smokers (P = 0.008). Conclusions: The association of smoking and age suggests that smoking may contribute to generate a field of injury that leads to lesions in shorter periods than other causes. The stronger relationship of smoking with lesions in the buccal mucosa and FOM than in the tongue suggests that tissue characteristics mediate the effects of tobacco. 相似文献
25.
BACKGROUND: Ecto-diadenosine polyphosphates are ubiquitous compounds with several physiological roles. Ecto-diadenosine polyphosphates hydrolase control their actions by degrading and terminating their signaling. The present work deals with the identification and partial characterization of ecto-diadenosine polyphosphates hydrolase on human prostasomes. METHODS: Reverse-phase and paired-ion HPLC techniques have been used. RESULTS: Prostasomes have an ecto-diadenosine polyphosphates hydrolase that leads to the degradation of several diadenosine compounds. Kinetic parameters of the enzyme show that diadenosine tetraphosphate is the preferred substrate that is further metabolized by the prostasome-ecto-nucleotidases to adenosine. The ecto-enzyme is bound to the prostasome-membranes through a GPI-anchor and is activated by physiological concentration of Ca+2, Mg+2, and Mn+2. Its optimum pH is also in the slightly alkaline physiological range. Human spermatozoa do not possess this hydrolytic activity, but they can acquire it after fusion with prostasomes. CONCLUSIONS: The existence of an enzyme capable of degrading diadenosine compounds and can be transferred to human spermatozoa suggests new physiological implications for the role of prostasomes in fertilization. 相似文献
26.
Zamfir CL Irimiea L Indrei A Indrei LL Trandafirescu M Carja L 《Revista medico-chirurgical?? a Societ????ii de Medici ??i Naturali??ti din Ia??i》2002,107(2):273-275
It seems that the particular intermediary disposal of zona fasciculata in the cortical ensemble of the adrenal gland is not insignificant, especially for the variability and for the glandular activities. Because of its specific cellular arrangement, displaying both positional and dimensional uniformity; it can be considered like a real islet of orderly cordonal symmetric tissue between two other cortical zones which present instead a very irregular cellular disposal. Distinct capsular fibrillar elements inserted around the cells and especially around small calibre vascular structures from zona fasciculata, are directly involved in the distribution of the secretory products. The concentration of the lipidic components is always more important at this cortical level than anywhere else in the whole adrenal gland, probably in connecting with the microsystem of channels from the entire surface of the zona fasciculata cells. 相似文献
27.
Solorzano CC Middleton LP Hunt KK Mirza N Meric F Kuerer HM Ross MI Ames FC Feig BW Pollock RE Singletary SE Babiera G 《American journal of surgery》2002,184(4):364-368
BACKGROUND: Intracystic papillary carcinoma (IPC) of the breast is a rare form of noninvasive breast cancer. An appreciation of associated pathology with IPC may be critical in surgical decision-making. METHODS: The medical records of all patients with IPC treated between 1985 and 2001 were retrospectively reviewed. Three patient groups were identified according to the pathologic features of the primary tumor: IPC alone, IPC with associated ductal carcinoma in situ (DCIS), and IPC with associated invasion with or without DCIS. Types of treatment and outcomes were compared between groups. RESULTS: Forty patients were treated for IPC during the study period. Fourteen had pure IPC, 13 had IPC with DCIS, and 13 had IPC with invasion. The incidence of recurrence and the likelihood of dying of IPC did not differ between the three groups regardless of the type of surgery (mastectomy or segmental mastectomy) performed and whether radiation therapy was administered. The disease-specific survival rate was 100%. CONCLUSIONS: When IPC is identified, it is frequently associated with DCIS and or invasion. Standard therapy should be based on associated pathology. The role of radiation therapy in pure IPC remains to be determined. 相似文献
28.
Chagpar A Middleton LP Sahin AA Meric-Bernstam F Kuerer HM Feig BW Ross MI Ames FC Singletary SE Buchholz TA Valero V Hunt KK 《Cancer》2005,103(8):1581-1586
BACKGROUND: The ideal pathologic assessment of sentinel lymph nodes (SLNs) in patients with breast carcinoma remains controversial. The authors evaluated how detailed assessment of SLNs using immunohistochemistry (IHC) and serial sectioning would affect treatment decisions and outcomes in patients with breast carcinoma who had negative SLNs on standard hematoxylin and eosin staining. METHODS: The SLNs from patients who were treated between June 1998 and June, 1999 and who had negative lymph node status determined by hematoxylin and eosin staining (n = 84 patients) were evaluated further with serial sectioning and cytokeratin IHC. Patients were offered adjuvant therapy based on primary tumor factors. RESULTS: The median patient age was 57 years, and the median tumor size was 1.2 cm. At a median follow-up of 40.2 months, 81 patients (96%) were alive with no evidence of disease, 1 patient was alive with disease, 1 patient had died of disease, and 1 patient had died of other causes. Fifteen patients (18%) had micrometastases identified on IHC. Of the total 84 patients, information regarding adjuvant therapy was not available for 5 patients. Of the remaining 79 patients, 10 patients (13%) were not offered adjuvant chemotherapy but had positive SLN status determined by IHC. SLN status based on IHC evaluation did not correlate with age (P = 0.077), tumor size (P = 0.717), grade (P = 0.148), estrogen receptor status (P = 1.000), or lymphovascular invasion (P = 0.274). Furthermore, IHC-detected positive SLN status did not correlate with distant metastasis (P = 0.372) or overall or distant metastasis-free survival (P = 0.543 and P = 0.540, respectively). CONCLUSIONS: Although the finding of SLN micrometastases by IHC may change management in > 12% of patients, preliminary results suggested that such micrometastases do not affect outcomes significantly. 相似文献
29.
Ovarian cancer is quite common in women, but brain metastases from ovarian cancer are considered rare. Eleven patients with solitary cerebral metastasis from ovarian epithelial carcinoma were treated at the Neurosurgical Department of University of Rome La Sapienza, between 1980 and 2000. We treated all of the 11 patients by surgical en bloc removal and by postoperative radiotherapy and chemotherapy. Mean survival was 28 months, and the cause of death was recurrence of the systemic disease in all cases. Multimodal treatment by surgery, radiation and chemotherapy is the best choice of treatment and leads to a median survival of about 20 months. 相似文献
30.