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 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 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 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 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.
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