| 1. |
- Blennow, Kaj, 1958, et al.
(författare)
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No association between the alpha2-macroglobulin (A2M) deletion and Alzheimer's disease, and no change in A2M mRNA, protein, or protein expression.
- 2000
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 0300-9564 .- 1435-1463. ; 107:8-9, s. 1065-79
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Tidskriftsartikel (refereegranskat)abstract
- A polymorphism consisting of a deletion near the 5' splice site of exon 18 on the alpha2-macroglobulin (A2M) gene (A2M-2) has been suggested to be associated with Alzheimer's disease (AD) in family-based studies. We studied the A2M-2 allele together with the ApoE alleles in a large series on patients with AD (n = 449) and age-matched controls (n = 349). Neuropathologically confirmed diagnoses were available in 199 cases (94 AD and 107 control cases). We found no increase in A2M-2 genotype or allele frequencies in AD (27.5% and 14.6%) versus controls (26.4% and 14.9%). In contrast, a marked increase (p < 0.0001) in ApoE epsilon4 genotype or allele frequencies was found in AD (66.6% and 41.2%) as compared with controls (29.8% and 16.5%), suggesting sufficient statistical power in our sample. No relation was found between the A2M-2 and the ApoE epsilon4 allele. No change in A2M exon 17-18 mRNA size or sequence or A2M protein size was found in cases carrying the A2M-2 deletion, suggesting that there is no biological consequences of the A2M intronic deletion. No change in A2M protein level in cerebrospinal fluid was found in AD, suggesting that the A2M-2 allele does not effect the A2M protein expression in the brain. The lack of an association between the A2M-2 allele and AD in the present study, and the lack of abnormalities in the A2M mRNA or protein suggest that the A2M-2 allele is not associated with AD.
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| 2. |
- Risberg, Björn, et al.
(författare)
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Dissociated expression of Bcl-2 and Ki-67 in endometrial lesions : diagnostic and histogenetic implications
- 2002
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Ingår i: International Journal of Gynecological Pathology. - Philadelphia, USA : Lippincott Williams & Wilkins. - 0277-1691 .- 1538-7151. ; 21:2, s. 155-160
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the present study was to analyze the expression of the proliferation marker, Ki-67, and the anti-apoptotic protein, bcl-2, in various endometrial lesions. Ki-67 and bcl-2 expressions were studied in 194 specimens of endometrial hyperplasia, polyps, carcinomas, and cyclic endometrium from a defined geographic area. Results were statistically analyzed with respect to marker expression, localization to the stromal or glandular component, and intraglandular topography. The lowest glandular Ki-67 expression was seen in secretory endometrium, in polyps, and in atypical hyperplasia. The Ki-67 score was significantly higher and less heterogeneous in endometrial carcinomas than in hyperplasia (p<0.001). Endometrial hyperplasia of all types was characterized by a markedly heterogeneous glandular expression of Ki-67. The glandular expression of bcl-2 was highest in proliferative endometrium and polyps. Bcl-2 expression was significantly lower in adenocarcinomas than in hyperplastic lesions (p=0.002). Ki-67 and bcl-2 expression showed a significant association in proliferative endometrium (p=0.003). Endometrial polyps demonstrated a unique pattern of very low expression of Ki-67 and high bcl-2 expression in both stroma and glands. Our findings indicate that an imbalance between proliferation and apoptosis may be an important factor in the development of different endometrial lesions, benign as well as malignant. The specific finding of inter- and intraglandular Ki-67 heterogeneity may be valuable as an adjunct to morphology in the differential diagnosis of endometrial hyperplasia.
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| 3. |
- Uggla, Bertil, 1962-, et al.
(författare)
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Expression of topoisomerase IIalpha in the G0/G1 cell cycle phase of fresh leukemic cells
- 2001
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Ingår i: Leukemia research. - Oxford, United Kingdom : Elsevier. - 0145-2126 .- 1873-5835. ; 25:11, s. 961-966
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase IIalpha (topoII alpha) is the target enzyme for several antineoplastic drugs. Correlation between low expression of topo IIalpha and drug resistance has been shown in vitro, but there is limited evidence of a correlation to initial response to treatment or to overall prognosis. Normal cells express topo IIalpha in S/G2/M phase of the cell cycle but not in G0/G1 phase. However, some data suggest that topo IIalpha could be expressed in G0/G1 phase in malignant cells. We have investigated the expression of topo IIalpha in leukemic cells from 25 patients with acute leukemia by flow cytometry, separating cells of different cell cycle phases. We demonstrated that 9/25 samples showed >50% positive cells in G0/G1, and another five samples showed >20%. This finding could possibly provide an explanation to previous difficulties in correlating topo IIalpha expression with clinical outcome. Six of eight patients, where >20% of the cells in G0/G1 were positive for topo IIalpha, entered CR, compared to one of five patients with <20% topo IIalpha positive cells in G0/G1. We suggest that topo IIalpha expression in G0/G1 in leukemic cells may be of predictive value for clinical response to cytostatic drugs.
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| 4. |
- Villman, Kenneth, et al.
(författare)
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Topoisomerase II-α expression in different cell cycle phases in fresh human breast carcinomas
- 2002
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Ingår i: Modern Pathology. - Baltimore : Lippincott Williams & Wilkins. - 0893-3952 .- 1530-0285. ; 15:5, s. 486-491
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Tidskriftsartikel (refereegranskat)abstract
- Topoisomerase II-alfa (topo IIalfa) is the key target enzyme for the topoisomerase inhibitor class of anti-cancer drugs. In normal cells, topo IIalfa is expressed predominantly in the S/G2/M phase of the cell cycle. In malignant cells, in vitro studies have indicated that the expression of topo IIalfa is both higher and less dependent on proliferation state in the cell. We studied fresh specimens from 50 cases of primary breast cancer. The expression of topo IIalfa in different cell cycle phases was analyzed with two-parameter flow cytometry using the monoclonal antibody SWT3D1 and propidium iodide staining. The expression of topo IIalfa was significantly higher in the S/G2/M phase of the cell cycle than in the G0/G1 phase in both DNA diploid and DNA nondiploid tumors. In 18 of 21 diploid tumors, and in 25 of 29 nondiploid tumors, >50% of the topo IIalfa–positive cells were in the G0/G1 phase. This significant expression of topo IIalfa in the G0/G1 phase of the cell cycle may have clinically important implications for treatment efficacy of topoisomerase II inhibitors.
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| 5. |
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| 6. |
- Stoltzfus, Patricia, et al.
(författare)
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Laminin-5 gamma2 chain expression facilitates detection of invasive squamous cell carcinoma of the uterine cervix.
- 2004
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Ingår i: International Journal of Gynecological Pathology. - : Lippincott Williams & Wilkins. - 0277-1691 .- 1538-7151. ; 23:3, s. 215-222
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Tidskriftsartikel (refereegranskat)abstract
- Because it has been suggested that laminin-5 can be used as a sensitive marker for epithelial cell invasion, specimens from patients with invasive squamous cell carcinoma of the uterine cervix with a previous history of preinvasive lesions were evaluated by a newly developed monoclonal antibody directed against the gamma2 chain of laminin-5. Thirty-two archival paraffin specimens consisting of the matched preinvasive and invasive lesions from 15 women were evaluated to determine whether gamma2 chain laminin-5 staining was present in lesions that progressed to invasive cancer. With the exception of one tumor (a small cell nonkeratinizing squamous carcinoma), all squamous cell carcinomas exhibited positive staining. Five of 17 preinvasive lesions also were immunoreactive for the laminin-5 protein. A blinded histologic reevaluation revealed invasion or lesions suspicious for invasion in four of five preinvasive lesions. Our findings suggest that laminin-5 determined by a monoclonal antibody facilitates the identification of invasive lesions that are difficult or impossible to identify on routinely stained histologic sections.
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