Browsing by Subject "Metallothionein"

Now showing 1 - 9 of 9
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    Clinicopathological 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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    Elevated metallothionein (MT) expression in invasive ductal breast cancers predicts tamoxifen resistance
    (Murcia : F. Hernández, 2005) Surowiak, P.; Matkowski, R.; Materna, V.; Györffy, B.; Wojnar, A.; Dziegiel, Piotr; Kornafel, Jan; Zabel, M.; Pudelko, Marek
    Elevated expression of the low molecular weight metallothionein (MT) proteins can be found typically in breast cancer cases with less favourable prognosis. The MT gene has been described to be potentially down-regulated by estrogen receptor alpha. The present study is aimed at examining the predictive value of MT expression for results of tamoxifen treatment in breast cancer in relation to steroid receptor status. Sixty patients with primary invasive ductal breast cancers with post-operative tamoxifen treatment were enrolled in the study. In paraffin sections of the studied tumours immmunohistochemical reactions were performed using antibodies directed against MT, estrogen receptors (ER) and progesterone receptors (PgR). Results of the immunohistochemical reactions and of clinical observations were analysed using multivariate progression analysis based on the Cox proportional hazard model. Elevated MT expression was demonstrated to be typical for cases with documented relapse of the disease (P<0.001) or terminated by death (P=0.03). Decreased ER expression was found to be typical for cases of a higher grade (P=0.02) and cases terminated by death (P=0.006). The multivariate analysis showed that elevated MT expression was characteristic for cases with shorter overall survival time (P=0.04). The data showed that MT carried an independent, and also independent from ER status, unfavourable predictive value as far as results of tamoxifen treatment were concerned.
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    lmmunohistochemical detection of metallothionein in carcinomatous and normal human gastric mucosa
    (Murcia : F. Hernández, 2000) Tuccari, G.; Giuffre, G.; Arena, F.; Barresi, G.
    Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT) expression has been immunohistochemically investigated in 112 formalin-fixed paraffin-embedded surgical gastric samples, 38 of which were early carcinomas (EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data (ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa) were also analysed; in addition, 22 biopsies of normal gastric mucosa were studied as tissue control. The MT immunoreactivity was evaluated by staining and intensity-distribution scores. A various MT positivity was appreciable in the cytoplasm and nucleus of antrum or body gastric epithelia1 cells in 100% of normal control biopsies. 751112 (67%) gastric carcinomas showed MT immunoreactivity with a significant lower expression in AGC. No relationships were encountered between MT immunostaining and clinico-pathological data; in addition, no difference in the Kaplan-Meier survival curves of patients with various MT expression was achieved. When the transitional mucosa was examined, 84/89 (94%) samples were stained although the immunoreaction was not always concordant with that encountered in adjacent carcinomatous elements. The significant statistical decrease of MT scores observed by us moving from normal to neoplastic gastric mucosa allows us to exclude the hypothesis of an overexpression of MT in gastric carcinomas.
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    lmmunohistochemical detection of metallothionein in liver, duodenum and kidney after dietary copper-overload in rats
    (Murcia : F. Hernández, 1998) Mullins, J.E.; Fuentealba, I.C.
    Metallothionein (MT) has been used in immunohistochemical techniques to indicate presence and distribution of heavy metals within biological tissues. This study describes a comparison of the pattern of MT-immunostaining in the liver, duodenum and kidney during dietary copper overload in rats. Sixteen male 10-week-old Wistar rats were randomly allocated into groups of four. Two groups were fed a pelleted diet containing 1,500 mgíkg copper and two control groups received a rodent diet containing 10 mgkg copper. After 6 weeks samples of liver, kidney and duodenum were collected for immunohistochemistry and histology. An indirect immunoperoxidase technique, using monoclonal antibody E9 against horse MT and polyclonal sera against rabbit MT, was employed. Copper-loaded rats had marked MT-immunoreactivity within the nucleus and cytoplasm of many periportal hepatocytes, renal proximal convoluted tubule epithelial cells, intestinal columnar epithelial cells and Paneth cells. Immunohistochemical staining was similar using either mouse anti-MT polyclonal serum, or monoclonal antibody E9. Hepatocytes surrounding inflammatory foci were positive for MT, supporting the proposed role of this protein in free radical scavenging. The presence of MTexcretion o€ copper-metallothionein (Cu-MT) in copperloaded rats. Paneth cells were easily detected using MTimmunostaining. MT may play a part in absorption of copper from intestinal contents and possible storage as CU-MT in Paneth cells. The function of Paneth cells remains unknown but the presence of marked MTimmunoreactivity in these cells, observed in copperloaded rats, suggests their involvement in homeostasis and metabolism o€ copper. in the kidney appears to be associated with renal
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    Mother-fetus transference of lead and cadmium in rats, involvement of metallothionein
    (Murcia : F. Hernández, 2009) Benitez, M.A.; Méndez Armenta, M.; Montes, S.; Rembao, D.; Sanin, L.H.; Rios, C.
    This study was designed to assess the effect of Cadmium (Cd) and lead (Pb) exposure during pregnancy in rats and their correlation with metallothionein (MT). Rats were exposed to either 10 ppm Cd or 300 ppm Pb through drinking water during pregnancy. Both metals were measured in placenta, fetus brain and fetal and maternal blood. MT was quantified in placenta and fetus brain and it was also observed in placenta by immunohistochemical technique. Offspring weight was found to be significantly lower for the Cd exposure group than for the control group. A Cd increase in the placenta of the exposed group was accompanied by MT induction; these effects were related to a limited accumulation of Cd in fetus brain. In contrast, dam Pb exposure caused an accumulation of Pb in the fetus brain and induced damage to placenta. The results account for differences in the transference of these metals during pregnancy that could be related to their toxicity.
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    Prognostic significance of augmented metallothionein (MT) expression correlated with Ki-67 antigen expression in selected soft tissue sarcomas
    (Murcia : F. Hernández, 2005) Dziegiel, Piotr; Salwa-Zurawska, W.; Zurawski, J.; Wojnar, A.; Zabel, M.
    In soft tissue sarcomas, the most important prognostic criteria include extent of malignancy (G), size of the tumour and intensity of Ki-67 antigen expression. In recent times expression of metallothionein (MT) in cells of some malignant processes of epithelial origin was found to correlate with intensity of Ki-67 antigen expression and to carry a possible prognostic significance. The present study aimed at a demonstration of prognostic value of MT expression and at comparing it with Ki-67 antigen expression and G grade in selected soft tissue sarcomas. Immunohistochemical studies were performed on paraffin sections in 54 cases of malignant fibrous histiocytoma (MFH), 18 cases of liposarcoma and 20 cases of synovial sarcoma. The extent of MT and Ki-67 antigen expression was evaluated and an attempt was made to correlate the results with each other and with grade of the tumour. Expression of MT was evident both in the cytoplasm and in cell nuclei of all studied sarcomas. The most pronounced MT expression was noted in MFH-type tumours. The extent of Ki-67 antigen expression was similar in MFH and liposarcoma and was the lowest in synovial sarcoma. In MFH, liposarcoma and synovial sarcoma a pronounced positive correlation was documented between expression of MT and Ki-67 antigen (r=0.85; p<0.001; r=0.93, p<0.0001; r=0.79, p<0.0001). In all types of the tumours a positive relation was detected between MT expression, expression of Ki- 67 and G grade of malignancy in the tumour. Moreover, patients with higher MT expression in the studied tumours demonstrated a shorter survival. MT expression in soft tissue tumours of MFH, liposarcoma and synovial sarcoma type strongly correlated with intensity of proliferation (Ki-67) and G grade and could be useful in defining the extent of malignancy and in prognostic appraisal in the tumours.
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    Prognostic significance of metallothionein expression in correlation with Ki-67 expression in adenocarcinomas of large intestine
    (Murcia : F. Hernández, 2003) Dziegiel, Piotr; Forgacz, J.; Suder, E.; Surowiak, P.; Kornafel, Jan; Zabel, M.
    The study aimed at determining levels of metallothionein (MT) and Ki-67 antigen expression in adenocarcinomas of large intestine and examining relation of the expression levels with various clinical and pathological variables. The studies were performed on 81 cases of large intestine adenocarcinoma. Using immunocytochemistry, expressions of MT (positive reaction in 73 cases) and of Ki-67 (positive reaction in 79 cases) antigen were examined and the obtained results were compared with, i.a., grade (G) of the tumour and depth to which intestinal wall was infiltrated by individual tumours. Patient survival analysis was also performed, as correlated to expression levels of the two antigens. The obtained results permitted to disclose that the lower was grade of histological differentiation (G2, G3), the more pronounced was expression of MT and Ki-67. Also, the deeper was neoplastic infiltration of intestinal wall, the more pronounced was MT and Ki-67 expression. Despite the relatively strong correlation between MT expression and Ki-67 expression (r=0.536; p<0.05), only Ki-67 antigen expression in large intestine adenocarcinomas was inversely correlated to survival of the patients. Ki-67 proved to be a better prognostic marker, as compared to MT, in large intestine adenocarcinomas.
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    The immunohistochemical expression of metallothionein in inflammatory bowel disease. Correlation with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices
    (Murcia : F. Hernández, 2003) Loachim, E.; Michael, M.; Katsanos, C.; Demou, A.; Tsianos, E.V.
    Metallothionein (MT) expression in intestinal resection specimens from 41 patients with ulcerative colitis (UC) and 10 patients with Crohn’s disease (CD ) was immunohistochemically studied by the avidin-biotin (ABC) method. In addition, the possible relationship of its expression with HLA-DR antigen expression, lymphocyte subpopulations and proliferation-associated indices was studied in order to elucidate the role of this molecule in inflammatory bowel disease (IBD). The MT immunoreactivity was recorded by staining and intensity-distribution scores. MT staining varied in and was mainly localized in the cytoplasm, although a combined nuclear/cytoplasmic reactive pattern was also seen in epithelial cells. MT expression was decreased in UC, and CD compared with normal mucosa. No difference in MT expression between UC and CD was noted. In UC, a gradually decreased expression from remission, to resolving and to active phase was observed. An inverse correlation of MT expression with HLA-DR antigen expression was detected (p=0.018) in the cases of UC. The data suggest that a low level of MT expression in inflammatory bowel disease and particularly in active phase of UC may indicate a decreased endogenous intestinal protection and it may be implicated in the pathogenesis of the disease.
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    Time-course expression of metallothioneins and tissue metals in chronic relapsing form of experimental autoimmune encephalomyelitis
    (Murcia: F. Hernández, 2011) Jakovac, Hrvoje; Grebic, Damir; Tota, Marin; Barac-Latas, Vesna; Mrakovčić-Šutić, Ines; Milin, Čedomila; Radosevic-Stasic, Biserka
    To elucidate the role of metallothioneins (MTs) in the pathomechanisms of autoimmune CNS disorders we estimated the expression of MTs I+II and the tissue concentrations of Zn2+ and Cu2+ in the brain, spinal cord (SC) and in the liver during the periods of attacks and remissions in chronic relapsing experimental autoimmune encephalomyelitis (CR-EAE). Disease was induced in the genetically susceptible Dark Agouti (DA) rats by subcutaneous injection of bovine brain homogenate in CFA. Control rats were treated with CFA. The data, obtained by clinical assessment, immunohistochemistry and inductivity coupled plasma spectrometry, have shown that during the first attack (on the 12th day) MTs I+II were markedly upregulated in subarachnoid regions and perivascular space on astrocytes, microglia and on spinal neurons. Simultaneously, the concentrations of zinc in the SC and zinc and copper in the liver have found to be increased. During the second attack (on the 22nd day) a new overexpression of MTs was found in the cerebellum, in sulcus hippocampi, in spinal neurons and particularly in hepatocytes around the central vein. Concomitantly, in the brain and SC the concentration of copper increased. The data point to a neuroprotective role of MTs and to an important regulatory role of essential metals and hepatic MTs in the pathogenesis of CR-EAE