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Mateja Legan

Publications and source records attributed to Mateja Legan.

7 recordsLinked to original sources

Expression of cyclooxygenase-2 is associated with p53 accumulation in premalignant and malignant gallbladder lesions.

AIM: To examine the relationship between cyclooxygenase-2 (COX-2) overexpression and p53 accumulation in gallbladder carcinoma and its precursor lesions. METHODS: Sixty-eight gallbladder tissue samples comprising 14 cases of normal gallblader epithelium, 27 cases of dysplasia (11 low-grade dyplasia and 16 high-grade dysplasia) and 27 adenocarcinomas were evaluated by immunohistochemistry for COX-2 expression and p53 accumulation. The relationship among COX-2 expression, p53 accumulation and clinicopathological characteristics was analysed. RESULTS: COX-2 was expressed in 14.3% of normal gallbladder epithelium, 70.3% of dysplastic epite hlium, and 59.2% of adenocarcinomas. When divided into low- and high-grade dysplasia, COX-2 was positive in 5 (45.4%) cases of low-grade and 14 (87.5%) of high-grade dysplasia (P = 0.019). Accumulation of p53 was detected in 5 (31.2%) cases of high-grade dysplasia and in 13 (48.1%) of carcinomas. No p53 accumulation was found in normal epithelium or low-grade dysplasia. COX-2 overexpression was observed in 17 of 18 (94.4%) cases with p53-accumulation in comparison with 20 (40.0%) out of 50 cases without p53 accumulation (P < 0.001). CONCLUSION: The significant differences in COX-2 expression among normal epithelium, low-grade dysplasia and high-grade dysplasia suggest that overexpression of COX-2 enzyme is an early event in gallbladder carcinogenensis. Furthermore, since accumulation of p53 correlates with COX-2 expression, COX-2 overexpression observed in gallbladder high-grade dysplasia and carcinoma might be partly due to the dysfunction of p53.

Adenocarcinoma↗

Cyclooxygenase-2 expression determines neo-angiogenesis in gallbladder carcinomas.

Neo-angiogenesis may have an important role in the poor prognosis of gallbladder carcinoma. An enhanced expression of COX-2 was found in precancerous lesions and in gallbladder carcinoma, likely to be involved in carcinogenesis as well as in angiogenesis. To study the relationships between the COX-2 expression and degree of vascularization, as well as to evaluate their role in the prognosis of patients with gallbladder carcinoma. 27 cases of gallbladder adenocarcinoma were included, classified grading I-III according the WHO classification. The COX-2 and endothelial antigen CD105 expressions were assessed immunohistochemically. COX-2 expression was evaluated according to the percentage and staining intensity of positive cells into "COX-2 positive" and "COX-2 negative" groups. In order to assess tumor microvessel density (MVD), CD105 positively stained microvessels were counted for each specimen in predominantly vascular areas (hot spots) at 200 x magnification. The MVD ranged from 9 to 46 microvessels/field. 15 tumors belonged to the hypervascular group (MVD > or = 25) and 12 to the hypovascular group. There were 16 (59.2%) COX-2 positive cases. There was difference in the degree of angiogenesis between COX-2 positive vs. COX-2 negative group: 11 (68.8%) out of 16 "COX-2 positive" tumors were hypervascular, in comparison with just 4 (36.4%) of "COX-2 negative" tumors. Our data show that the MVD corresponds to the COX-2 overexpression in gallbladder carcinomas. Augmented tumor neovascularization induced by COX-2 might be responsible for the poor prognosis in gallbladder carcinoma patients.

Adenocarcinoma↗

Chlamydia pneumoniae infection in Slovenian patients with diffuse coronary artery disease.

Chlamydia pneumoniae (CP) infection might be involved in the pathogenesis of various forms of coronary artery disease (CAD), but there are no data about diffuse CAD with clinical picture of stable angina pectoris. Authors in a prospective study determined serum CP antibody levels (with MIF test) of 71 patients with coronarographically proven diffuse CAD and compared them to the age matched control group of the healthy Slovenian population. After azithromycin treatment in patients with chronic CP infection or reinfection, the CP antibody levels were determined again. A high percentage of chronic infection with CP was demonstrated (83.1%), and almost half (46.5%) of patients with diffuse CAD had reinfection or reactivation of chronic infection. A significantly higher prevalence of chronic CP infection was found in patients with diffuse CAD than in the healthy population (83.1% vs. 15.9%, p< 0.0001). After treatment with azithromycin, IgA seronegativity was achieved in 17.3%, in 23.1% the titer was lowered, however, in 57.7% of patients no change of antibody titers was found. In conclusion, a high prevalence of chronic infection with CP was found in patients with diffuse CAD. With azithromycin therapy, the eradication of chronic infection is difficult to achieve as well as to prove.

Adult↗

Apoptosis and histopathologic changes in diffuse coronary atherosclerosis.

The aims of the study were to investigate the histopathologic characteristics of atherosclerotic lesions and to evaluate the role of apoptosis or programmed cell death in diffuse coronary atherosclerosis. The study included 59 patients who underwent coronary artery bypass grafting coupled with coronary endarterectomy because of diffuse coronary atherosclerosis. Histopathologic analysis of endarterectomy sequesters showed atheroma with confluent extracellular lipid core-type IV lesions in 13 cases (22%); atheroma with lipid core and a cap of fibromuscular layers-type V lesions in 9 cases (15.3%); predominantly calcified fibrous tissue-type VII lesions in 13 cases (22%); and predominantly fibrous tissue-type VIII lesions in 24 cases (40.7%). TUNEL-positive cells were observed in 4 endarterectomy sequesters (6.8%) of subjects with diffuse coronary atherosclerosis. TUNEL-positive cells were demonstrated in the area of mononuclear infiltrates as well as in the vessel wall. The percentage of TUNEL-positive cells in mononuclear infiltrates was 0.5%. Intense mononuclear infiltrates in tunica intima were found in 50% of sequesters, and they consisted of macrophages (40%), T-lymphocytes (17%), and B-lymphocytes (14%). In the area of infiltrates the proportion of MIB-1-positive cells was 2.7%, which was higher than in the intima outside the area of infiltrates (0.5%). In conclusion, apoptosis, which is confined to mononuclear infiltrates, is most likely involved in the development of diffuse coronary atherosclerosis; however, the percentage of apoptotic cells was low (0.5%). A higher proportion of apoptotic cells in the area of infiltrates compared to the rest of the intima was associated with a higher proportion of MIB-1-positive cells. Atherosclerotic lesions in diffuse coronary atherosclerosis were advanced, with a predominance of type VII to VIII lesions.

Aged↗

Histopathologic signs for the inflammatory role of Chlamydia pneumoniae in the high-grade atherosclerotic coronary artery wall.

The aim of the study was to prove the long-lasting and continuously harmful effect of chronic Chlamydia pneumoniae (CPn) infection on vessel walls in patients with diffuse coronary artery disease (CAD). In surgically obtained endarterectomized atherosclerotic plaques grade VI-VIII (Stary classification) from 10 patients with diffuse coronary artery disease and chronic (7) or past (3) CPn infection, signs of inflammatory response of the vessel wall on infectious agents were studied. In all 10 endarterectomized plaque step serial sections, immunologic signs of vessel wall response were present (positive T- and B-lymphocytes, macrophages, and capillarogenesis). In 8 of 10 patients' atherosclerotic plaque, unique features of active vasculitis in the neoarteriolar wall as well as arteriologenesis, were found. Seven of these 8 patients had serologically proven chronic CPn infection, and 1 had past infection. Features of vasculitis as well as arteriologenesis were absent in 2 patients who recovered from CPn infection at the time of surgery. In the endarterectomized segments of 3 randomly chosen patients in this study, the polymerase chain reaction method revealed positive DNA of CPn. Two of these patients had chronic infection, but the third had only a past CPn infection. This study provides evidence that CPn infection has continuous and a long-lasting inflammatory response in the high-grade atherosclerotic coronary artery vessel wall.

B-Lymphocytes↗