Histology and histopathology Vol.16, nº 2 (2001)
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- PublicationOpen AccessProtein kinase CK2 signal in neoplasia(Murcia : F. Hernández, 2001) Tawfic, S.; Yu, S.; Wang, H.; Faust, R.; Davis, A.; Ahmed, K.Protein kinase CK2 (previously known as casein kinase 11) is a protein serinelthreonine kinase that has been implicated in cell growth and proliferation. The focus of this review is on the apparent role of CK2 in cancer. Studies from severa1 laboratories have shown a dysregulated expression of the kinase in tumors. Nuclear matrix and chromatin appear to be key sites for signaling of the CK2 activity in relation to cell growth. Severa1 types of growth stimuli produce a common downstream response in CK2 by enhancing its nuclear shuttling. The neoplastic change is also associated with changes in intracellular localization of the kinase so that a higher nuclear localization is obsewed in tumor cells compared with normal cells. Experimental studies suggest that dysregulated expression of the a subunit of CK2 imparts an oncogenic potential in the cells such that in cooperation with certain oncogenes it produces a profound enhancement of the tumor phenotype. Recent studies have provided evidence that overexpression of CK2 in tumor cells is not simply a reflection of tumor cell proliferation alone but additionally may reflect the pathobiological characteristics of the tumor. Of considerable interest is the possibility that CK2 dysregulation in tumors may influence the apoptotic activity in those cells. Approaches to interfering with the CK2 signal may provide a useful means for inducing tumor cell death.
- PublicationOpen AccessNeuronal and mixed neuronal glial tumors associated to epilepsy. A heterogeneous and related group of tumours(Murcia : F. Hernández, 2001) Moreno, A.; Felipe, J.de; García Sola, R.; Navarro, A.; Ramón y Cajal, S.The group of brain tumors with mature components encompasses severa1 pathological entities including: the ganglioneuroma; the gangliocytoma; the ganglioglioma; the desmoplastic ganglioglioma; the neurocitoma and a group of glioneuronal hamartomatous tumorous lesions, such as meningoangiomatosis. The dysembryoplastic neuroepithelial tumor is characterized by the presence of multiple cortical nodules made up of small, oligo-like cells and a myxoid pattern rich in mucopolysaccharides. Mature neuronal cells are frequently detected throughout the tumor. Most of them are associated with microhamartias in the adjacent brain and pharmacoresistant epilepsy. The excellent prognosis of the majority of these tumors and the potential for malignant transformation of the glial component in the ganglioglioma are the two most remarkable findings. Histological signs of anaplasia and greater mitotic and proliferative activities are associated with local recurrences. Atypical neurocytomas occur only exceptionally. Treatment choices are surgical resectioning and, in those cases presenting greater proliferative activity and cytological atypia, postoperative radiotherapy rnay be recornmended. This paper reviews this heterogeneous group of neoplasms and hamartomatous lesions, pointing out presumable transitions among the different types of mixed neuronal and glial brain tumors. A single term of "mixed neuronal-glial tumors" is defended, distinguishing different subgroups of tumors, depending on the predominant cellular component.
- PublicationOpen AccessHuman skin reconstruct models: A new application for studies of melanocyte and melanoma biology(Murcia : F. Hernández, 2001) Berking, C.; Herlyn, M.Studies of melanocyte and melanoma biology using monocultures of cells are limited because of culture-induced morphology changes and expression of genes related to growth, migration, and invasion, which do not reflect the in situ phenotype of normal melanocytes, nevus cells, or melanoma cells from biologically early progression stages. The development of organotypic cultures of human skin, in which culture artifacts are greatly diminished and cell-matrix and cellcell interactions between different cell types can be investigated in a three-dimensional system, has opened a new era for melanoma research. Long-term in vivo studies, especially important for melanomagenesis and melanoma metastasis have become possible through grafting of skin reconstructs to immuno.deficient laboratory animals. In this review, principles and different methods of skin reconstruction are introduced with focus on the application for pigment cell biology
- PublicationOpen AccessMlBl proliferation index in breast infiltrating carcinoma: Comparison with other proliferative markers and association with new biological prognostic factors(Murcia : F. Hernández, 2001) González-Vela, M.C.; Garijo, M.F.; Fernández, F.; Val-Bernal, José FernandoAims: In breast invasive carcinoma our objectives were 1) to compare cellular proliferation determined by MIBl index with S-phase fraction (SPF) assessed by flow cytometry and with mitotic index, and 11) to examine the association of MIBl index with classical and with new biological prognostic factors [bcl- 2, p53, c-erbB-2 and cathepsin D (CD)]. Methods and results: From 102 cases of breast invasive carcinoma, 5- pm thick serial sections were cut from formalin-fixed, paraffin-embedded tissue blocks, and processed for detection of CD, c-erbB-2, p53, bcl-2, Ki-67 antigen MIB-1 and estrogen receptors (ER) and progesterone receptors (PR). SPF was measured by flow cytometry in fresh-frozen tissue samples taken from the carcinoma in each patient. MIBl index was correlated with SPF (rho=0.45, pe0.0001) and with mitotic index (rho=0.42, p<0.0001). The MIB-1 index was positively associated with the histological grade (p=0.001), tumor size (p=0.04) and the presence of metastases in axillary lymph nodes (p=0.01). MIBl was associated directly with p53 @=0.045) and inversely with bcl-2 @=0.0002). The MIB-1 index was not statistically associated with cerbB- 2. There was a weak association between MIBl index and stromal cell CD. The median MIBl index was higher in tumors with moderate to strong CD staining of stromai cell, but the difference did not reach statistical significance (p=0.09). Conclusions: MIBl index correlates with well established methods for assessing tumor proliferation and with parameters of an aggressive phenotype of tumor. MIBl index is an effective and readily accessible method for assessing tumor proliferation in breast carcinoma.
- PublicationOpen AccessEarly acquisition of bowel segment-specific Bcl-2 homolog expression profiles during development of the human ileum and colon(Murcia : F. Hernández, 2001) Vachon, P.H.; Cardin, E.; Harnois, C.; Reed, J.C.; Plourde, A.; Vézina, A.The adult small and large intestines display distinct expression profiles of Bcl-2 homologs, known regulators of apoptosis. This is thought to indicate that control mechanisms of intestinal apoptosis are gut segment-specific. Little is known on the expression of Bcl-2 homologs during gut development. In man, intestinal features and functions are acquired largely by mid-gestation (18-20 wks); the question whether segment-specific controls of intestinal apoptosis are also acquired early during development remains open. In the present study, we approached this by investigating the expression of six Bcl-2 homologs (Bcl-2, Bcl-XL, Mcl- 1, Bax, Bak, Bad), and one nonhomologous associated molecule (Bag-1), during development of the human ileum and colon (12-20 wks of gestation). Beginning at 18 wks, we found that the epithelial localization of Bcl-2 homologs displayed differential patterns (or gradients) in both the ileum and colon; however, the patterns of some of the homologs differed between the two segrnents. For instance, Bag-1 and Bcl-2 exhibited crypt-villus decreasing gradients of expression in the ileum but not in the colon, whereas Mcl-1 displayed differing compartimentalizations between the two segments. Further analyses indicated that the steady-state expression levels of Bcl-2 homologs underwent modulations between 12 and 20 wks; however, the obsewed developmental profiles contrasted significantly between the two segments. For example, Bcl-2, Bag-1 and Bak levels increased in the colon, but the levels of these same homo.logs decreased in the ileum. Furthermore, by 18-20 wks, we found that the expression levels of each Bcl-2 homolog analyzed differed greatly between the ileum and colon. Altogether, these data indicate that the expression of Bcl-2 homologs is modulated differentially during human gut development in order to establish, by midgestation, distinct expression profiles for the small and large intestines. This in turn suggests that gut segmentspecific control mechanisms of human intestinal apoptosis are acquired early during fetal life.