Histology and histopathology Vol.23, nº8 (2008)
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- PublicationOpen AccessEPH receptors in cancer(Murcia : F. Hernández, 2008) Castaño, Julio; Davalos, Verónica; Schwartz Jr., Simo; Arango, DiegoEPH receptors and their ephrin ligands constitute the largest sub-family of receptor tyrosine kinases (RTKs) and are components of cell signaling pathways involved in animal development. The ability of the EPH/ephrin guidance system to position cells and modulate cell morphology underlies their various roles in development. In addition, EPH signaling plays an important role in oncogenic processes observed in several organs. These receptors are involved in a wide range of processes directly related with tumorigenesis and metastasis, including cell attachment and shape, migration, and angiogenesis. Accordingly, deregulation of EPH expression and signaling activity could be crucial for the tumorigenic process. This review focuses on EPH receptors’ roles in oncogenic transformation and tumor progression.
- PublicationOpen AccessLocalization of influenza virus sialoreceptors in equine respiratory tract(Murcia : F. Hernández, 2008) Scocco, Paola; Pedini, VeraThis study was performed to identify the equine respiratory tract areas which express the specific receptor for equine influenza virus; findings may be useful to provide new ways to treat the infectious disease. The present work aims to visualize in situ the presence of sialoderivatives in the horse respiratory tract in order to localize sialoderivatives acting as influenza virus receptors. To this purpose, nasal mucosae, trachea, bronchus and lung parenchyma were removed from 8 mature horses of both sexes. We performed sialic acid characterization by means of mild and strong periodate oxidation and saponification, combined with lectin histochemistry and sialidase digestion, in addition to the direct evidentiation of sialic acid residues. No differences were shown between sexes. Sialic acid residues are present in the nasal mucous cell secretion, where they are linked to galactose by means of a2-3 linkage and are mainly C9 acetylated, and in the nasal and tracheal epithelial lining, where they are represented by periodate labile residues (a2-3)- and/or (a2-6)- linked to galactose. Specific receptors for equine influenza viruses are present at the nasal and tracheal epithelial lining cell coat levels, and in some trachea epithelial cells, but the horse possesses a preventive defence, which consists of the secretion of a mucous layer at nasal level, which could specifically inactivate the hemagglutinins of equine influenza virus; in addition, it expresses other sialoreceptors which can mask the influenza specific ones.
- PublicationOpen AccessExpression of K+ channels in normal and cancerous human breast(Murcia : F. Hernández, 2008) Brevet, Marie; Ahidouch, Ahmed; Sevestre, Henri; Merviel, Philippe; El Hiani, Yassine; Robbe, Micheline; Ouadid-Ahidouch, HalimaPotassium (K+) channels contribute to the regulation of cell proliferation and apoptosis and are also involved in tumor generation and malignant growth. Using immunohistochemical analysis, we investigated the expression of four K+ channels GIRK1 (G-Protein Inwardly Rectifying Potassium Channel 1), Ca2+-activated K channel (KCa1.1), voltage activated K+ channels (KV 1.1 and KV 1.3) and of the anti-apoptotic protein Bcl2 in normal and cancerous breast tissues and compared their expression with clinicopathological data. GIRK1 was overexpressed in carcinomatous tissues. In contrast, KV 1.1 and KV 1.3 were less expressed in cancerous tissue. The expression of Bcl-2 was similar in both tissues. As to the clinicopathological data, a correlation between KCa1.1 channel and estrogen receptor (ER) expression was observed. GIRK1 was overexpressed in breast carcinoma suggesting its involvement in proliferation and oncogenesis and its possible use as a putative pharmaceutigal target. The correlation between KCa1.1 channel and ER suggests the involvement of this channel in proliferation. The loss of expression of the two channels KV 1.1 and KV 1.3 may correspond to their role in apoptosis.
- PublicationOpen AccessApolipoprotein D expression absence in degenerating neurons of human central nervous system(Murcia : F. Hernández, 2008) Navarro, Ana; Ordóñez, Cristina; Martinez, Eva; Pérez, Cristina; Astudillo, Aurora; Tolivia, JorgeApolipoprotein D (apo D), a lipocalin transporter of small hydrophobic molecules could play an important role in several neurodegenerative diseases. However, its role in those diseases remains unclear. There has been reported increments of apo D in relation with different neuropathologic diseases. Recently, we reported the absence of apo D in neurons of substantia nigra which can contribute to the lability of neurons to oxidative damage. In order to determine the relationship between apo D expression and neuronal death, we studied the expression of apo D in various regions of human brains from patients without any neurological or psychological disorders, in relation with the neuronal damage revealed by Fluoro-Jade B staining. The absence of expression for apo D in injured neurons and the negative staining for Fluoro-Jade B of neurons that express apo D was observed in all sections studied. These findings are in accordance with the role possibly played by apo D in the neuroprotection of the nervous system.
- PublicationOpen AccessClinicopathological significance of MMP-2 and its specific inhibitor TIMP-2 in gastric cancer(Murcia : F. Hernández, 2008) Alakus, H.; Grass, G.; Hennecken, J.K.; Bollschweiler, E.; Schulte, C.; Drebber, U.; Baldus, S.E.; Metzger, R.; Hölscher, A.H.; Mönig, S.P.Matrix metalloproteinases (MMPs) can degrade type IV collagen of extracellular matrices and basal membranes and thus play a key role in the migration of malignant cells. In vivo, MMPs are inhibited by tissue inhibitors of metalloproteinases (TIMPs). Since in a previous study we showed that the expression of MMP-2 correlates with clinicopathological parameters in gastric cancer, we have now investigated a possible correlation of MMP-2 and TIMP-2 expression with survival in gastric cancer, as well as the possible association of TIMP-2 with clinicopathological parameters. Tissue samples were obtained from 116 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. MMP-2 and TIMP-2 expression was analysed using immunohistochemical staining and was graded semiquantitatively (score 0 – 3). High epithelial MMP-2 immunoreactivity was significantly associated with tumor stage and poor survival using the Kaplan-Meier log-rank statistical method (log-rank statistics). However, using Cox regression analysis, high epithelial MMP-2 immunoreactivity was not an independent prognostic factor. TIMP-2 showed no association with survival in gastric cancer, but the intensity of TIMP-2 staining in tumor cells correlated significantly with tumor differentiation based on the WHO and Lauren and Ming classifications, as well as with presence of distant metastasis. Our results show that high epithelial MMP-2 expression in gastric cancer is associated with poor survival, although it is not an independent prognostic factor, and that aggressive forms of gastric cancer are associated with low TIMP-2 expression.
- PublicationOpen AccessRECK, a novel matrix metalloproteinase regulator(Murcia : F. Hernández, 2008) Meng, N.; Li, Y.; Zhang, H.; Sun, X-F.Extracellular matrix (ECM) macromolecules are important for creating the cellular environments required during development and morphogenesis of tissues. Matrix metalloproteinases (MMPs) are a family of Zn-dependent endopeptidases that collectively are capable of cleaving virtually all ECM substrates, and play an important role in some physiological and pathological processes. MMP activity can be inhibited by some natural and artificial inhibitors. A newly found membrane-anchored regulator of MMPs, the reversioninducing- cysteine-rich protein with kazal motifs (RECK), is downregulated when the cells undergo a process of malignant transformation, and is currently the subject of considerable research activity because of its specific structure and function. In this review, we have chosen to concentrate our efforts on the structure, function, regulation, and future prospect of RECK in order to provide a new target for prevention and treatment of tumours.
- PublicationOpen AccessCell adhesion molecules in stromal corneal dystrophies(Murcia : F. Hernández, 2008) Nemeth, Gabor; Felszeghy, Szabolcs; Kenyeres, Annamaria; Szentmáry, Nora; Berta, Andras; Süveges, Ildiko; Módis, LaszloThe aim of the present study was to investigate the expression pattern of different cell adhesion molecules in corneal stromal dystrophies. Fifteen corneal buttons from patients diagnosed with three different types of stromal corneal dystrophies and healthy corneas were investigated. Paraffin embedded sections were stained immunohistochemically with monoclonal antibodies against human intercellular adhesion molecule-1 (ICAM-1), endothelial selectin (Eselectin) and endothelial cadherin (E-cadherin) using the avidin-biotin-peroxidase-complex technique. The sections were compared to normal eye bank controls. In corneas from granular dystrophy patients ICAM-1 was expressed focally in epithelial cells and in keratocytes, and expressed diffusely in endothelial cells. In corneas from macular dystrophy patients diffuse epithelial staining was observed and the stromal and endothelial expression was found to be similar to that of granular dystrophy. In lattice dystrophy, only the epithelial cells and endothelium were intensively positive for ICAM-1. E-selectin was not present on any layer of the corneal specimens. E-cadherin was observed only in the epithelium of all three types of corneal dystrophies. Normal corneas did not express any of the investigated adhesion molecules. We found different expression patterns of adhesion molecules in corneas from stromal dystrophies. Our results suggest that adhesion molecules may be involved in the pathogenesis of corneal stromal dystrophies.
- PublicationOpen AccessDevelopmental pattern of three vesicular glutamate transporters in the myenteric plexus of the human fetal small intestine(Murcia : F. Hernández, 2008) Linke, N.; Bódi, N.; Resch, B.E.; Fekete, Eva; Bagyánszki, M.Three vesicular glutamate transporters (VGLUT1-3) have previously been identified in the central nervous system, where they define the glutamatergic phenotype, and their expression is tightly regulated during brain development. In the present study we applied immunocytochemistry to examine the distribution of the immunoreactivity of all three VGLUTs during prenatal development of the myenteric plexus in the human small intestine. We also investigated changes in their localization in the different segments of the small intestine and in the different compartments of the developing myenteric ganglia. Immunoreactivity against all three VGLUTs was found predominantly in the ganglionic neuropil, interganglionic varicose fibers and perisomatic puncta, but cytoplasmic labeling with different intensities also occurred. Each transporter displayed a characteristic spatiotemporal expression pattern, with the transient increase or decrease of immunoreactive cell bodies, varicosities or perisomatic puncta, depending on the fetal age, the gut segment or the ganglionic compartment. Throughout gestational weeks 14-23, VGLUT1 immunoreactivity always predominated over VGLUT2 immunoreactivity, though both peaked around week 20. VGLUT3 immunoreactivity was less abundant in the developing myenteric plexus than those of VGLUT1 and VGLUT2 immunoreactivity. It was mainly expressed in the ganglionic neuropil and in the perisomatic puncta throughout the examined gestational period. Neuronal perikarya immunoreactive for VGLUT3 were restricted to between weeks 18 and 20 of gestation and exclusively to the oral part of the small intestine.
- PublicationOpen AccessDefect of the cerebellar vermis induced by prenatal y-ray irradiation in radiosensitive BALB/c mice(Murcia : F. Hernández, 2008) Saito, Aya; Yamauchi, Hirofumi; Ishida, Yuka; Ohmachi, Yasushi; Nakayama, HiroyukiThe developing fetal brain is one of the most susceptible organs to irradiation insult. Prenatal irradiation-induced abnormalities in the cerebrum have been well examined in mouse fetuses. However, little information on abnormalities in the cerebellum caused by irradiation is available. Moreover, few reports have examined the chronological changes of the brain from the prenatal to the postnatal period. To analyze the chronological changes induced by irradiation, we exposed pregnant mice to g-ray irradiation on embryonic day 13.5 (E13.5) and investigated the histopathology of the cerebellum at several time points from E14.5 to postnatal day 28. BALB/cA mice were used, which is a radiosensitive strain, and C57BL/6J, which is a radioresistant strain. The irradiated BALB/c showed a remarkable vermis deficit after birth, and histological analysis demonstrated that there were severe losses of the external germinal layer (EGL) and Purkinke cell layer. TUNEL analysis shoed that apoptosis was strongly induce in the cerebellar anlage of the irradiated BALB/c compared to the C57BL/6J at E14.5. Immunohistochemical analysis revealed a significat decrease of phospho-histone H3 positive EGL cells in the irradiated BALB/c at E18.5 and E0, indicating that irradiation causes a decrease in the number of mitotic cells. The results suggest that the strong induction of apoptosis in radiosensitive BALB/c led to a decrease of proliferation activity in the cerebellar anlage during embryonic development, and consequently, severe cerebellar abnormality was evoked.
- PublicationOpen AccessStructural and functional insights into nucleocytoplasmic transport(Murcia : F. Hernández, 2008) Beck, Martin; Medalia, OhadThe cell nucleus is surrounded by a double membrane system, the nuclear envelope (NE), with the outer nuclear membrane being continuous with the endoplasmic reticulum. Nuclear pore complexes (NPCs) fuse the inner and outer nuclear membranes, forming aqueous channels that allow free diffusion of small molecules but that also mediate the energy-dependent transport of large macromolecules. The NPC represents the largest known molecular complex and is composed of about 30 different proteins, termed nucleoporins (Nups). Here, we review recent studies that provide novel insight into the structural and functional organization of nucleocytoplasmic transport. In addition, prospects towards a high resolution model of the nuclear pore are discussed.
- PublicationOpen AccessPrognostic index expression of cyclin-D1, cerbB-2 and VEGF metastases vs corresponding primary cancers and metastatic vs non-metastatic adenocarcinomas(Murcia : F. Hernández, 2008) Roger Parra, Edwin; Young Park, Ji; Midori Saito, Dalva; Yae Takagaki, Teresa; Ribeiro Rodrigues, Olavo; Capelozzi, Vera LuizaThe prognostic relevance of different molecular markers in lung cancer is a crucial issue still worth investigating, and the specimens collected and analyzed represent a valuable source of material. Cyclin- D1, c-erbB-2 and vascular endothelial growth factor (VEGF) have shown to be promising as prognosticators in human cancer. In this study, we sought to examine the importance of Cyclin-D1, c-erbB-2 and VEGF, and to study the quantitative relationship among these factors and disease progression in metastases vs corresponding primary cancer, and metastatic vs non metastatic cancers. Material and Methods: We used immunohistochemistry and morphometric analysis to evaluate the amount of tumour staining for Cyclin-D1, cerbB- 2 and VEGF in 52 patients with surgically excised ademocarcinoma of the lung, and the outcome for our study was survival time until death from hematogenic metastases. Results: Metastasis presented lower c-erbB-2 expression than corresponding primary cancers (p=0.02). Cyclin-D1 and VEGF expression were also lower in metastases than in corresponding primary cancers, but this difference did not achieve statistical significance. Non-metastatic cancers also presented significantly lower Cyclin-D1 and c-erbB-2 expression than metastatic cancers (p<0.01 and p<0.01, respectively). Equally significant was the difference between higher cerbB- 2 expression by metastatic cancers compared to non-metastatic cancers (p=0.02). Considering survival in Kaplan-Maier analysis, Cyclin-D1 (p=0.04), c-erbB-2 (p=0.04) and VEGF (p<0.01) were important predictors of survival in metastatic cancers.