Histology and histopathology Vol.27, nº 7 (2012)

Ir a Estadísticas

Permanent URI for this collection

http://hdl.handle.net/10201/177621

Browse

Now showing 1 - 5 of 13

Open Access
Farnesoid X Receptor (FXR) from normal to malignant state
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Koutsounas, Loannis; Giaginis, Constantinos; Theocharis, Stamatios
The Farnesoid X Receptor (FXR) is a member of the nuclear receptor superfamily of ligand-activated transcription factors, which plays crucial role in bile acid, cholesterol, lipid and glucose metabolism, as well as in the development of atherosclerosis, intestinal bacterial growth and liver regeneration. FXR is also involved in the pathogenesis of cholestatic diseases, non-alcoholic fatty liver disease and inflammatory bowel disease. Recent evidence further suggests a key role for FXR in apoptosis and cancer. Notably, FXR deficiency promoted intestinal inflammation and tumorigenesis, suggesting that FXR activation might be a promising strategy in the treatment of colon cancer. FXR deficiency in mice led to the development of spontaneous hepatocarcinomas, while FXR inhibition might represent a novel therapeutic approach in Barett’s esophagus. In breast cancer cell lines, FXR agonists down-regulated the breast cancer target gene aromatase. FXR inhibited Leydig tumor growth and progression, supporting evidence that FXR may be an important regulator of androgen homoeostasis. Further studies are required in order to establish possible antitumor effects of this nuclear receptor. Either reactivating or inhibiting FXR expression may represent promising therapeutic strategies in the treatment of certain types of human cancer
Open Access
Compartment- and malignance-dependent up-regulation of γ-glutamyltranspeptidase and dipetidylpeptidase-IV activity in human brain gliomas
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Mares, V.; Stremeňová, J.; Lisá, V.; Kozáková, H.; Marek, J.; Syrůček, M.; Šoula, O.; Sedo, A.
γ-Glutamyltranspeptidase (GGT, syn. γ-Glutamyltransferase) and dipeptidylpeptidase-IV (DPP-IV) activity participates in metabolic and growth control of normal and tumor cells by processing biologically active peptides. Here, we report on up-regulation of these enzymes in human brain gliomas determined by catalytic enzyme histochemistry and immunocytochemistry. Higher activity of GGT was found in 50%, 68% and 81% of WHO grade II, III and IV tumors, respectively. The process started at/near the microvasculature, from where it spread to the parenchyma. On average, the enzyme activity in grade II, III and IV gliomas exceeded controls 2.0, 3.0 and 3.5-fold, respectively. Up-regulation of DPP-IV-like activity also started at the microvasculature, but mainly in pericytes and mononuclear-like cells around the vessels and dispersed in the parenchyma. Marked elevation of this enzyme activity, comprising also tumor parenchyma, occurred only in grade IV glioblastomas (65% patients; 3.6 times above controls) which can, therefore, help in their differentiation from grade III gliomas. The increase of total DPP-IV-like activity also included its two enzymatic homologs, the canonical DPP-IV/CD26 and FAP-1α. The increase in GGT is supposed to be a tumor grade dependent response of microvasculature and tumor astrocytes to stress induced by tissue hypoxia and/or the metabolic aberrancies. The increase in DPP-IV-like activity in high-grade tumors can be attributed to inflammatory/scavenging processes performed by the mononuclear-like cells and, in glioblastomas, also to regressive changes in the structure and function of the microvasculature and tumor parenchyma, including astrocyte stress response. The inverse relationship between DPP-IV-like activity and Ki67 in most glioblastomas and shorter survival time of patients with low activity of this enzyme also suggest its anti-oncogenic effects
Open Access
Expression of basal cell keratin 15 and keratin 19 in oral squamous neoplasms represents diverse pathophysiologies
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Khanom, Rumana; Sakamoto, Kei; Kumar Pal, Samir; Shimada, Yasuyuki; Morita, Kei-ichi; Omura, Ken; Miki, Yoshio; Yamaguchi, Akira
Human epithelium contains keratin, which is expressed during differentiation. Depending on the target cell type, different types of keratin are expressed, and their alterations seem to represent changes in cell properties. The basal cells of oral epithelium express keratin 5 (K5), K14, K15 and K19, but their alterations in tumors are unclear. To address this issue and to seek possible diagnostic application, we examined the expression of these keratins in oral squamous cell carcinoma (OSCC) and squamous intraepithelial neoplasm (SIN). cDNA microarray analysis of 43 OSCC revealed slight upregulation of KRT14, downregulation of KRT15 and KRT19, and unaltered KRT5 expression. There were great variations in KRT15 and KRT19 expression across each cancer. Well-differentiated OSCC tended to express more KRT15 and less KRT19 compared to moderately- or poorly-differentiated OSCC. KRT15 was positively correlated with differentiation-related keratin, KRT13. These observations were further investigated by immunohistochemical examination. K5 and K14 were ubiquitously expressed in all 50 OSCC and 50 SIN examined. K15 and K19 were generally downregulated, but were considerably retained in about half of the cases and showed diverse expression patterns. K15-positive cancers tended to show a well-differentiated phenotype, and K19-positive cancers tended to show more invasive tumor fronts. Most K19-positive cancers appeared to develop with little associating SIN. K19 was consistently downregulated in SIN, while K15 was downregulated mainly in high grade SIN. In summary, K15 and K19, unlike K5 or K14, are expressed variably in both SIN and OSCC, which reflects the differences in their pathogenesis and biological behaviors, suggesting their prospective applications as markers for subclassifying OSCC and SIN
Open Access
Arterial carbon dioxide partial pressure influences CYP4A distribution in the rat brain
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Qi, Li; Meng, LiWei; Li, YiFei; Qu, Yi
PaCO2 is an important factor in the regulation of cerebral circulation, and it is often used to reduce intracranial pressure through hyperventilation during neurosurgery. Changes in concentration can cause changes in CBF (cerebral blood flow). 20-HETE is a product of CYP4A-mediated AA (arachidonic acid) metabolism and is a powerful endogenous vasoconstrictor; however, its effect on cerebral vasoconstriction in cats, dogs and rats remains to be confirmed. It is known that changes in PaCO2 can influence the expression of CYP4A in the rat brain, demonstrating the important role of 20-HETE in the mechanism of CO2-mediated cerebrovascular reactivity. Thirty healthy adult male Wistar rats that weighed between 200 g and 250 g were randomly divided into three groups (A, B, and C; n=10): group A, normocapnia (PaCO2 was maintained at approximately 40-45 mmHg); group B, hypocapnia (PaCO2 was maintained at approximately 20-25 mmHg); and group C, hypercapnia (PaCO2 was maintained at approximately 60-65 mmHg). Physiological parameters, including HR (heart rate), MBP (mean blood pressure), PH and PaCO2 were recorded every 30 min, and there were no significant hemodynamic or body temperature differences. The head was removed after 3.5 h to investigate brain CYP4A by immunohistochemistry. Relative to group A, group B exhibited the following changes: an increased pH, decreased PaCO2, and increased brain CYP4A protein expression (P<0.05). In contrast, group C exhibited decreased PH, increased PaCO2 and decreased CYP4A protein expression (P<0.05). CO2 can decrease the expression of brain CYP4A during hypercapnia and increase its expression during hypocapnia
Open Access
Widespread epithelioid angiosarcoma with ventricular wall involvement in a dog
(F. Hernández y Juan F. Madrid. Universidad de Murcia. Departamento de Biología Celular e Histología, 2012) Gázquez, A.; Martín de las Mulas, J.; Millán Ruiz, Y.; Garcia, A.; Masot, A.J.; Redondo, E.
This paper reports on a canine angiosarcoma, presenting as an “undifferentiated metastasizing tumor”. A 14-year-old female Cocker Spaniel was referred to the University of Extremadura Veterinary Clinic for clinical examination after suffering rapid deterioration, with chronic cough, anorexia and cachexia. One week after clinical examination, the dog died of right congestive heart failure and ventricular arrhythmia. Blood counts revealed lymphopenia and platelet depletion. The biochemistry profile was within normal limits, except for a drop in blood urea nitrogen. Cytological evaluation of liver and spleen biopsies revealed clustered anaplastic cells that lacked convincing tissue differentiation. Major findings at necropsy were enlarged spleen and multiple, beige to dark-red nodules ranging from 0.5 to 3 cm in diameter in the heart, lung, liver and spleen. At histological examination, multiple nests of anaplastic epithelioid cells were found in sections from all affected organs. Immunohistochemistry revealed widespread expression of CD31 and Factor VIII-related antigen. The neoplastic cells were negative for CD 18. The diagnosis of epithelioid angiosarcoma, localized in the myocardium, lung, liver and spleen was made. The primary site of the neoplasm could not be determined

Browse

Recent Submissions