Histology and histopathology Vol.21, nº 4 (2006)
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- PublicationOpen AccessExpression of checkpoint kinase 2 in breast carcinomas, correlation with key regulators of tumor cell proliferation, angiogenesis, and survival(Murcia : F. Hernández, 2006) Ribeiro-Silva, A.; Koyota Moutinho, M.A.; Becker de Moura, H.; Ribeiro do Vale, F.; Zucoloto, S.Checkpoint kinase 2 (Chk2) is a cell-cyclecheckpoint kinase that may act as a tumor suppressor gene due to its important role in DNA damage signaling and cell cycle regulation. The role of Chk2 expression in mammary tumorigenesis, however, is still poorly understood. This study was designed to assess the relationship between the expression of Chk2 and wellestablished prognostic factors, including disease-freesurvival and overall survival; and several regulators of cell proliferation and invasiveness in breast carcinomas, including oncogenes, tumor suppressor genes, apoptosisrelated proteins, and angiogenesis-related markers. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of not otherwise specified invasive ductal carcinomas. Clinical data were retrieved from medical files. In normal mammary parenchyma adjacent to the tumors Chk2 stained the nuclei of epithelial cells. Downexpression of Chk2 protein was observed in 23 carcinomas and correlated with advanced disease. Among the regulators of tumor cell proliferation and invasiveness analyzed, the downexpression of Chk2 correlated only with reduced expression of p27 and telomerase. There was no difference between the overall survival and disease-free survival rates according to Chk2 status. In conclusion, Chk2 correlated with reduced expression of h-TERT and p27, but not with angiogenic factors. Chk2 expression also did not interfere in the outcome of the patients.
- PublicationOpen AccessApolipoprotein D expression in substantia nigra of Parkinson disease(Murcia : F. Hernández, 2006) Ordóñez, Cristina; Navarro, A.; Pérez, C.; Astudillo, Aurora; Martinez, E.; Tolivia, J.Apolipoprotein 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. Increments of apo D have been reported in relation with injury and degeneration in the nervous system. Recently increases of apo D level have been reported in schizophrenia, a neuropathologic disease where the oxidative stress and lipid abnormalities may be involved. Apo D could act as a sequestering molecule binding excess of arachidonic acid in cells. In order to determine the relationship between apo D expression and other neurodegenerative pathologies related to oxidative damage, we studied the presence of apo D in the substantia nigra of control and Parkinson disease (PD) subjects. We found dopaminergic neurons were not immunoreactive for apo D, control or PD subjects. However, surrounding glial cells showed immunostaining for apo D and signal increases in PD cases. These findings support the role of apolipoprotein D in neuroprotection and the importance of glia in the amount of this protein in the central nervous system
- PublicationOpen AccessNitric oxide, a biological double-faced janus- Is this good or bad?(Murcia : F. Hernández, 2006) Thippeswamy, T.; McKay, J.S.; Quinn, J.P.; Morris, R.Nitric oxide (NO) is a biological messenger molecule produced by one of the essential amino acids L-arginine by the catalytic action of the enzyme NO synthase (NOS). The dual role of NO as a protective or toxic molecule is due to several factors, such as; the isoform of NOS involved, concentration of NO and the type of cells in which it is synthesised, the availability of the substrate L-arginine, generation of guanosine 3,5’- cyclic monophosphate (cGMP) from soluble guanylate cyclase and the overall extra and intracellular environment in which NO is produced. NOS activation as a result of trauma (calcium influx) or infection leads to NO production, which activates its downstream receptor sGC to synthesise cGMP and/or leads to protein nitrosylation. This may lead to one or more systemic effects including altered neurotransmission which can be protective or toxic, vaso/bronchodilatation in the cardiovascular and respiratory systems and enhanced immune activity against invading pathogens. In addition to these major functions, NO plays important role in thermoregulation, renal function, gastrointestinal motility, endocrine function, and various functions of the urogenital system ranging from renin secretion to micturation; spermatogenesis to penile erection; and ovulation to implantation and parturition. A schematic summary of the functions of NO and the various isoforms of NOS expressed in body systems is shown in figure 1. In this review, the historical background, biochemistry and biosynthesis of NO and its enzymes together with the mechanism of NO actions in physiology and pathophysiology are discussed.
- PublicationOpen AccessThe effect of oestradiol and neta on immunohistochemical staining of iNOS and eNOS in coronary arteries of ovariectomized rats(Murcia : F. Hernández, 2006) Koyuncu, F.M.; Ozbilgin, K.; Kuscu, N.K.; Inan, S.; Vatansever, S.; Ceylan, E.Aim: The postmenopausal period is associated with increased risk for coronary atherosclerosis, and the effect of hormone replacement therapy in reducing this risk is controversial. Previous studies reported that nitric oxide synthetase (NOS) level might be important for the development of atherosclerosis, but no study has shown the interaction between hormone replacement therapy and endothelial NOS and inducible NOS intensity on coronary arteries yet. Our goal was to find out the immunostaining intensity of endothelial NOS and inducible NOS in ovariectomized rats which received oestradiol and norethisterone treatment. Methods: We performed bilateral ovariectomy in 15, female, 90-day-old Wistar rats with an average weight of 250 grams. After waiting for 4 weeks for the menopausal state, they were divided into 3 groups to receive either placebo, 0.1 mg/day 17-ßoestradiol (group E2), or 0.1 mg/day 17-ß-oestradiol + 0.1 mg/day norethisterone acetate (group E2-NETA) for 5 weeks. Another group included 5, normal, adult, female intact rats and served as controls. At the end of the treatment, all rats were sacrificed and coronary arteries were stained with inducible NOS and endothelial NOS polyclonal antibodies using streptavidin-biotin technique. Results: The immunostaining of inducible NOS was prominent in perivascular connective tissue of the ovariectomized group but not in the control group. The inducible NOS immunostaining immunoreactivity was not detected in either treated groups. Immunostaining intensity of endothelial NOS did not differ in any 4 groups with similar staining. Conclusion: The present findings indicate that hormone replacement therapy down-regulates iNOS expression in coronary arteries of ovariectomized rats, and reduced iNOS may likely be involved in estrogen’s beneficial effects.
- PublicationOpen AccessClinicopathological study of metallothionein immunohistochemical expression, in benign, borderline and malignant ovarian epithelial tumors(Murcia : F. Hernández, 2006) Zagorianakou, N.; Stefanou, D.; Makrydimas, G.; Zagorianakou, P.; Briasoulis, E.; Karavasilis, V.; Pavlidis, N.; Agnantis, N.J.Metallothioneins (MTs) are a family of cystein-rich metal-binding proteins, which are expressed in normal cells during fetal and postnatal life but also in a variety of human neoplasms. MT expression in human tumors has been linked to resistance to anticancer drugs and differentiation and progression in some types of tumors. This study examined the immunohistochemical expression of MTs in benign, borderline and malignant tumors of ovarian surface epithelium and the possible correlations with clinicopathological parameters and survival. A total of 87 cases with diagnosis of ovarian surface epithelial tumors were included. Specifically, 21 cases of benign cystadenomas (11 serous and 10 mucinous), 14 borderline (low malignant potential tumors, 8 mucinous and 6 serous) and 52 cases of ovarian cancer were analysed. Immunohistochemical expression of MT (cut-off level >10% of tumor cells) was clearly associated with malignancy. A statistically significant correlation was found between the expression of MT in cancer cases and benign tumors (p<0.0001) and cancer cases and borderline tumors p= 0.003. In cancer cases a difference was observed between grade I and III (p=0.002). There was no correlation of MT overexpression with survival in the small number of ovarian carcinoma patients where it was analysed. MT constitutes a marker that characterizes aggressiveness and a high malignant potential in ovarian epithelial tumors. In diagnostic problems MT may help distinguish between benign, borderline and malignant tumors.
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