Histology and histopathology Vol.21, nº 3 (2006)
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- PublicationOpen AccessHistopathological changes in the brain of mouse fetuses by etoposide-administration(Murcia : F. Hernández, 2006) Nam, C.; Woo, G.H.; Uetsuka, K.; Nakayama, Hiroyuki; Doi, K.Etoposide (VP-16), a topoisomerase II inhibitor, is an anti-tumor agent which is also known to show embryotoxicity, and teratogenicity when administered to pregnant rodents. We examined VP-16- induced histopathological changes in the brain of mouse fetuses. Pregnant mice were intraperitoneally injected with VP-16 (4 mg/kg) on day 12 of gestation (GD 12), and fetuses were collected from 1 to 48 hours after treatment (HAT). Mitotic neuroepithelial cells in the telencephalic wall prominently decreased at 2 HAT, and were hardly observed at 4 HAT. The number of pyknotic neuroepithelial cells in the fetal brain began to increase at 4 HAT, and became prominent from 8 to 24 HAT. These pyknotic cells were also positively stained by TUNEL method, which can detect fragmented DNA, and showed ultrastructural characteristics of apoptosis. Additionally, these cells were also positive for cleaved caspase-3, an essential executioner of apoptosis. This indicated that excessive neuroepithelial cell apoptosis was induced in the brain of mouse fetuses following VP- 16 treatment on GD 12.
- PublicationOpen AccessMechanisms underlying estrogen-induced sexual differentiation in the hypothalamus(Murcia : F. Hernández, 2006) Ohtani-Kaneko, R.Estrogen plays critical roles in the sexual differentiation of the developing brain and genderspecific regulation of reproductive neuroendocrinology. Of the different regions of the brain, it is well known that hypothalamic areas contain key sexually differentiated neuronal circuits. Estrogen receptor (ER) proteins localized in the nucleus affect the expression of target genes when bound to their ligand estrogen. However, recent studies suggest that this may not be the only mechanism of estrogen action. Instead, estrogen can influence various cellular events through regulating different signaling pathways. Cross-talk between direct effects of estrogen on gene transcription and its effects on signaling pathways should be examined in future to elucidate mechanisms underlying sexual differentiation in the hypothalamus.
- PublicationOpen AccessHER-2 status determination in breast carcinomas. A practical approach(Murcia : F. Hernández, 2006) Garcia-Caballero, Tomas; Menéndez, M.D.; Vázquez-Boquete, A.; Gallego, R.; Forteza, J.; Fraga, M.Accurate evaluation of HER-2 status is crucial in the selection of breast carcinoma patients for trastuzumab (Herceptin) treatment. Various laboratory methods have been used for this purpose. The aim of the present work was to analyse the results obtained in the routine practice by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) in determination of HER-2 status. Five hundred and three cases of breast invasive ductal carcinoma were selected to analyse the HER-2 overexpression by immunohistochemistry (HercepTest, Dako). HercepTest 2+ equivocal cases (60) were studied by FISH (PathVysion, Vysis) to determine HER-2 gene amplification. HER-2 overexpression determined by Herceptest was shown in 97/503 cases (19%). FISH performed on equivocal cases demonstrated HER-2 amplification in 11/60 tumours (18%). IHC and FISH together showed HER-2 overexpression / gene amplification in 21% of breast invasive carcinomas. Immunohistochemical determination of HER-2 status represents an easy and standardized method that (in contrast to FISH) can be performed in all pathology laboratories without need of any special microscope and enabling to check the morphologic features of the cells analysed. However, in order to assure the reliability of the results, standardization of fixation protocols, automation of the immunohistochemical procedure, and training of pathologists in the interpretation of the results (scoring criteria) should be a priority. Equivocal HercepTest cases must be analysed by FISH preferably in a reference laboratory.
- PublicationOpen AccessGut-trophic feed additives and their effects upon the gut structure and intestinal metabolism. State of the art in the pig, and perspectives towards humans(Murcia : F. Hernández, 2006) Domeneghini, C.; Di Giancamillo, A.; Arrighi, S.; Bosi, G.The correct functional development of the gastrointestinal tract is of special importance during the neonatal and weaning phases of reared piglets. Nutrition is obviously a critical determinant in the growth of the gut in the young swine. The mucosal epithelium of the small intestine is reputed anatomically and functionally immature in neonatal pigs, a feature that appears to be exacerbated at weaning, when a colonization of the gut occurs by “new” microrganisms entering the alimentary canal with the solid feed. This frequently exposes piglets to diarrhoeic syndromes and other intestinal disturbances. Functional feed additives, also called nutraceuticals, appear as promising alternative substances to the use of chemotherapeutics as growth promoters in the rearing farm, above all considering the near banning of them by the European Parliament in the view of reducing antibiotic resistance phenomena in human therapies. Several feed additives are available that may play a role in the pig nutritional plan because of their trophic and cyto-protective effects on the gastrointestinal apparatus. Paying special attention to the quantitative consequences (histometry) upon the gut of the examined dietary supplements, this review, even if not fully exhaustive, will focus on the function (and possibly the mechanism/s of action) of certain guttrophic nutrient substrates. This in turn will sustain the potential use of these substances in human therapy, especially the one directed at resolving intestinal diseases, both in adult and infant ages. In nutritional studies as well as in other biomedical research fields, the swine is an excellent animal model.
- PublicationOpen AccessAdvances in molecular classification of renal neoplasms(Murcia : F. Hernández, 2006) Yin-Goen, Q.; Dale, J.; Yang, W.L.; Phan, J.; Moffitt, R.; Petros, J.A.; Datta, M.W.; Amin, M.B.; Wang, M.D.; Young, A.N.Kidney neoplasms are classified by light microscopy using the World Health Organization (WHO) system. The WHO system defines histopathologic tumor subtypes with distinct clinical behavior and underlying genetic mutations. In adults, the common malignant subtypes are variants of renal cell carcinoma (RCC). Histopathologic classification is critical for clinical management of RCC, but is becoming more complex with recognition of novel tumor subtypes, development of procedures yielding small diagnostic biopsies, and emergence of molecular therapies directed at tumor gene activity. Therefore, classification systems based on gene expression are likely to become essential for diagnosis, prognosis and treatment of kidney tumors. Recent DNA microarray studies have shown that clinically relevant renal tumor subtypes are characterized by distinct gene expression profiles, which are useful for discovery of novel diagnostic and prognostic biomarkers. In this review, we summarize the WHO classification system for renal tumors, general applications of microarray technology in cancer research, and specific microarray studies that have advanced knowledge of renal tumor diagnosis, prognosis, therapy and pathobiology.
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