Histology and histopathology Vol.25,nº12 (2010)

Ir a Estadísticas

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    Reduced expression of the membrane skeleton protein beta1-spectrin (SPTBN1) is associated with worsened prognosis in pancreatic cancer
    (Murcia : F. Hernández, 2010) Jiang, Xiaohua; Gillen, Sonja; Esposito, Irene; Giese, Nathalia A.; Michalski, Christoph W.; Friess, Helmut; Kleeff, Jörg
    Spectrins are members of the superfamily of F-actin cross linking proteins that are important as scaffolding proteins for protein sorting, cell adhesion, and migration. In addition, spectrins have been implicated in TGF-beta signaling. The aim of the present study was to analyze the expression and localization of beta1-spectrin (SPTBN1) in pancreatic tissues. mRNA levels of SPTBN1 in cultured pancreatic cancer cell lines, as well as in normal pancreatic tissues (n=18), chronic pancreatitis (n=48) and pancreatic cancer tissues (n=66) were analyzed by real time quantitative RT-PCR. Localization of SPTBN1 in pancreatic tissues was determined by immunohistochemistry. SPTBN1 staining was assessed semi-quantitatively in 55 cancer tissues and survival analysis was carried out using the KaplanMeier method. Median SPTBN1 mRNA levels were 6.0- fold higher in pancreatic cancer tissues compared to the normal pancreas (p<0.0001) and 2.2–fold higher compared to chronic pancreatitis tissues (p=0.0002). In the normal pancreas, SPTBN1 was present in the cytoplasm of normal ductal cells and occasionally in pancreatic acinar and centroacinar cells. In pancreatic cancer tissues, SPTBN1 was present in the cytoplasm of pancreatic cancer cells. Low SPTBN1 protein expression indicated a tendency for worsened prognosis with a median survival of 14.0 months, versus 23.8 months for patients whose tumors expressed moderate/high levels of SPTBN1. In conclusion, reduced SPTBN1 expression correlated with shorter survival of pancreatic cancer patients, suggesting a tumor suppressor function of this gene, as has already been shown for other malignancies of the gastrointestinal tract.
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    Epiprofin-Sp6. A new player in the regulation of tooth development
    (Murcia : F. Hernández, 2010) Jimenez-Rojo, Lucia; Ibarretxe, Gaskon; Aurrekoetxea, Maitane; de Vega, Susana; Nakamura, Takashi; Yamada, Yoshihiko; Unda, F.
    Odontogenesis is governed by a complex network of intercellular signaling events between the dental epithelium and mesenchyme. This network leads to the progressive determination of tooth shape, and to the differentiation of these tissues into enamel-producing ameloblasts and dentin-producing odontoblasts respectively. Among the main signaling pathways involved in the regulation of tooth development, Bone Morphogenetic Protein (BMP), Sonic hedgehog (Shh) and Wingless-type MMTV integration site (Wnt) pathways have been reported to play significant roles. Recently, the phenotype of mice deficient in Epiprofin/Sp6 (Epfn) has been found to present striking dental abnormalities, including a complete lack of differentiated ameloblasts and consequently no enamel, highly altered molar cusp patterns and the formation of multiple supernumerary teeth. In this article, we review the interaction of Epfn with the BMP, Shh and Wnt pathways in the regulation of tooth development, based on the data obtained from the study of several genetically modified mice.
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    New determinates of disease progression and outcome in metastatic ovarian carcinoma
    (Murcia : F. Hernández, 2010) Davidson, Ben; Reich, Reuven; Trope, Claes G.; Wang, Tian-Li; Shih, Ie-Ming
    Ovarian cancer is the most lethal gynecologic malignancy. This is attributed to frequent presentation at late stage, when the tumor has metastasized, as well as to development of chemotherapy resistance along tumor progression. Patients with advanced-stage ovarian carcinoma have widespread intraperitoneal metastases, including the formation of malignant serous effusions within the peritoneal cavity. Pleural effusions constitute the most frequent site of distant metastasis (FIGO stage IV disease). Unlike the majority of solid tumors, particularly at the primary site, cancer cells in effusions are not amenable to surgical removal, and failure in their eradication is one of the main causes of treatment failure. Our research in recent years has demonstrated that a large number of cancer-associated molecules are differentially expressed in effusions compared to primary carcinomas and solid metastases. We have additionally observed that expression of several of these molecules differs between primary diagnosis (prechemotherapy) and disease recurrence (postchemotherapy) specimens, and that they are significantly associated with response to chemotherapy and patient survival. These observations are thought to be related to disease progression, as well as to the unique microenvironment of effusions, and may have impact on the selection of targeted therapy in this cancer. This review discusses our recent observations with respect to the biology of ovarian carcinoma cells in effusions, and focuses on the clinical role of tumor-associated molecules at this anatomic site.
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    Tryptase, CD15 and IL-15 as reliable markers for the determination of soft and hard ligature marks vitality
    (Murcia : F. Hernández, 2010) Turillazzi, Emanuela; Vacchiano, Giuseppe; Luna Maldonado, Aurelio; Neri, Margherita; Pomara, Cristoforo; Rabozzi, Roberto; Riezzo, Irene; Fineschi, Vittorio
    In forensic practice, it is required to distinguish between suicidal or accidental hanging and simulated hanging. Conventional macroscopic and histological findings may be unreliable; vital signs are often absent, and they can be produced postmortem. The application of immunohistochemical techniques opened up a new field of investigation in the issue of ligature marks. We investigated the immunohistochemical expression of a panel of cytokines and inflammatory cells in skin specimens in autopsy cases of death due to hanging, to discuss their significance in assessing whether hanging mark and signs occurred before or after the death of the victim. We selected 21 cases in which broad, soft and yielding materials were used and 28 cases in which materials used for hanging were hard. The control group included the following 21 cases: 14 cases of sudden cardiac death and 7 cases of postmortem hanging (suspension) of bodies (drug overdose or suffocation as cause of death in all the cases). An immunohistochemical investigation of skin samples was performed utilizing antibodies anti-tryptase, fibronectin, TNFα, IL-6, IL-8, IL-10, MCP-1, IL-15, IL-1ß, CD45, CD4, CD3, CD8, CD68, CD20, CD15. We conclude that tryptase, IL-15, and CD15 appear to be reliable parameters in the determination of ligature marks’ vitality with the accuracy needed for forensic purposes. This fact especially applies to soft marks which are particularly difficult to evaluate on the basis of gross examination and of conventional histological studies.
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    Gill alterations as biomarkers of chronic exposure to endosulfan in Bufo bufo tadpoles
    (Murcia : F. Hernández, 2010) Brunelli, Elvira; Bernabò, Ilaria; Sperone, Emilio; Tripepi, Sandro
    Endosulfan sprayed on agricultural fields accumulates in temporary pools due to surface runoff or sediment transport and may result in high water concentrations in spring and summer, coinciding with breeding and crucial stages of amphibian larval development. In the present study, Bufo bufo tadpoles were exposed to three different concentrations of endosulfan (0.01, 0.05 and 0.1 mg/L) until they reached complete metamorphosis. The aim of the study was to investigate the effects of endosulfan, at environmentally relevant concentrations on gill morphology and ultrastructure. Modifications in ultrastructure and cell composition were observed at all concentrations after 96 h. The main gill effects recorded in treated animals were: mucous secretion, the appearance of tubular vesicles cells (TVC) and a degeneration phenomenon. Comparing these results with our previous findings in which we used growth, developmental rate and behaviour as endpoints, we also demonstrated that the first effect of endosulfan on Bufo bufo was gill alteration, thus supporting the role of a morphological approach in toxicological studies. This study provides additional information on the role of morphological studies in demonstrating the effects of exposure to environmental pollutants. In this context, the use of amphibian gills, as effective biomarkers, is a valuable approach in evaluating exposure to agrochemicals.