| 1. |
- 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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| 2. |
- Graflund, Marianne, et al.
(författare)
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Immunohistochemical expression of p53, bcl-2, and p21WAF1/CIP1 in early cervical carcinoma : Correlation with clinical outcome
- 2002
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Ingår i: International Journal of Gynecological Cancer. - Malden, USA : BMJ. - 1048-891X .- 1525-1438. ; 12:3, s. 290-298
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to assess the value of p53, bcl-2, and p21WAF1/CIP1 immunoreactivity as predictors of pelvic lymph node metastases (LNM), recurrences, and death due to the disease in early stage (FIGO I-II) cervical carcinomas. FIGO stage, type of histopathology, and tumor grade were also evaluated in this series of patients treated by radical hysterectomy (Wertheim-Meigs) between 1965 and 1990. A total of 172 patients were included. A tumor was regarded as positive when more than 30% of the neoplastic cells exhibited immunoreactivity. Positive immunostaining was found in 8.9% for p53, in 43.5% for bcl-2, and in 25.0% for p21WAF1/CIP1. None of them was able to predict LNM or clinical outcome. Presence of LNM, tumor recurrence, and death from disease were significantly associated with the FIGO stage (P = 0.014, P = 0.009, and P = 0.001, respectively). The 5-year cancer-specific survival rate was 91.6% and the overall survival rate was 90.5%. It was concluded that immunohistochemically detected p53, bcl-2, and p21WAF1/CIP1 appeared to be of no predictive value with regard to LNM, tumor recurrences, or long-term survival in early cervical carcinomas.
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| 3. |
- Jahnson, Staffan, et al.
(författare)
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Tumor mapping of regional immunostaining for p21, p53, and mdm2 in locally advanced bladder carcinoma
- 2000
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Ingår i: Cancer. - New York, USA : John Wiley & Sons. - 0008-543X .- 1097-0142. ; 89:3, s. 619-629
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of this study was to elucidate the associations among immunostaining for p53, p21, and mdm2; their respective expression within each tumor; and the value of these variables for predicting treatment outcome after cystectomy for patients with locally advanced bladder carcinoma.Methods: The hospital records from all 173 patients treated with cystectomy for locally advanced urothelial bladder carcinoma between 1967 and 1992 were retrospectively reviewed. Three consecutive sections from biopsies taken before any treatment were stained using the standard immunohistochemical technique for p53, p21, and mdm2, respectively. The cutoff limit was 20% or more for positive p53 expression and 10% or more for positive p21 and mdm2 expression.Results: Positive immunostaining was observed for p53 in 98 tumors (57%), for p21 in 89 tumors (51%), and for mdm2 in only 16 tumors (9%). The only association found between immunostaining for the three antibodies was that most mdm2-positive tumors had positive p21 expression. Tumor mapping of regional immunostaining showed no association between immunostaining for p53 and p21. In a proportional hazards analysis, no association was found between the results of immunostaining for the three antibodies and treatment outcome.Conclusions: Positive or negative expression of p53, p21, or mdm2, or combinations of these, was not associated with cancer specific mortality after cystectomy for bladder carcinoma. There was no association between immunostaining for p21 and p53, whereas positive immunostaining for mdm2 was observed in a minority of the tumors. These results indicate that, in addition to p21, p53, and mdm2, there are other oncoproteins and tumor suppressor proteins along the p53 pathway that are involved in tumor development and progression.
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| 4. |
- Robinson, Yohan, 1977, et al.
(författare)
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An optimized method for the assay of the red blood cell--age-related enzyme aspartate aminotransferase.
- 2004
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Ingår i: Laboratory hematology : official publication of the International Society for Laboratory Hematology. - 1080-2924 .- 1523-6528. ; 10:3, s. 144-6
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Tidskriftsartikel (refereegranskat)abstract
- Three methods of preparation of red blood cell concentrate for erythrocyte aspartate aminotransferase measurement were compared: (1) filtration of whole blood through a cellulose column (n = 36); (2) washing of whole blood and aspiration of buffy coat after centrifugation (n = 48); (3) optimized method with washing without aspiration of buffy coat (n = 229).
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| 5. |
- Asp, Julia, 1973, et al.
(författare)
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Alterations in the regulatory pathway involving p16, pRb and cdk4 in human chondrosarcoma.
- 2001
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Ingår i: Journal of orthopaedic research : official publication of the Orthopaedic Research Society. - 0736-0266. ; 19:1, s. 149-54
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Tidskriftsartikel (refereegranskat)abstract
- The G1 regulatory pathway involving p16, pRb and cdk4 in the cell cycle has been investigated in human chondrosarcoma. The protein expression of p16, pRb and cdk4 was analyzed by Western blot in cultured cells from eight chondrosarcomas and in two chondrosarcoma cell lines. Both cell lines and one other sample were negative for p16. Moreover, one of the cell lines was pRb-negative and showed a high expression of cdk4 as well. In the other cell line and in three other samples pRb of expected size were detected in addition to a shorter form of the protein. To further investigate the reasons for down-regulation of the p16 protein, the p16-coding gene CDKN2 was analyzed by polymerase chain reaction (PCR), methyl-specific PCR (MSP) and sequencing in all tumor samples as well as in corresponding tumor tissues from three of the samples. The p16-negative samples were all found to have homozygous deletion of CDKN2. Another sample showed partial gene methylation and a heterozygous position in codon 148 was detected in one sample. The same base substitution was also found in two of the tissue samples. Finally, cytogenetic analysis of the samples with homozygously deleted CDKN2 revealed multiple structural abnormalities in all three cases. In conclusion, the p16/pRb/cdk4 pathway may play an important role in the pathogenesis of some chondrosarcomas.
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| 6. |
- Asp, Julia, 1973, et al.
(författare)
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Changes of the p16 gene but not the p53 gene in human chondrosarcoma tissues.
- 2000
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 85:6, s. 782-6
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Tidskriftsartikel (refereegranskat)abstract
- The role of two important tumour suppressor genes, p16 and p53, was evaluated in cartilaginous tumour tissues. Genomic DNA from 22 chondrosarcomas, 5 benign chondroid tumours, 1 sample of reactive proliferative cartilage and 2 samples of normal cartilage were analysed using polymerase chain reaction, single strand conformational polymorphism, DNA sequencing and methylation-specific polymerase chain reaction. The p16 gene was found to be partly methylated in 5 high-grade chondrosarcomas and homozygously deleted in 1 chondrosarcoma. Moreover, a polymorphism was detected in 3 malignant tumours, but not in benign tumours or normal cartilage. Analysis of the p53 gene revealed an unchanged structure in all samples. These findings show a role for p16, but not p53, in chondrosarcoma.
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| 7. |
- Tsui, Janice C. S., et al.
(författare)
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Localization of nitric oxide synthase in saphenous vein grafts harvested with a novel "no-touch" technique : potential role of nitric oxide contribution to improved early graft patency rates.
- 2002
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Ingår i: Journal of Vascular Surgery. - New York, USA : Elsevier. - 0741-5214 .- 1097-6809. ; 35:2, s. 356-362
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The use of the saphenous vein in coronary artery bypass graft surgery is associated with high 1-year occlusion rates of as much as 30%. A new "no-touch" technique of saphenous vein harvesting in which the vein is harvested with a pedicle of surrounding tissue and not distended may result in improved early patency rates. We hypothesize that nitric oxide synthase is better preserved with the no-touch technique, and the aim of this study was the investigation of whether nitric oxide synthase distribution and quantity in saphenous veins harvested with the no-touch technique differ from those veins harvested with the conventional technique. The separate contribution of perivascular tissue removal and distension to alterations in nitric oxide synthase was also studied.Methods: Segments of 10 saphenous veins were harvested from 10 patients who underwent coronary artery bypass grafting surgery with the no-touch and conventional techniques. Samples were also taken from segments that were stripped of surrounding tissue but not distended. Nitric oxide synthase distribution was studied with reduced nicotinamide adenine dinucleotide phosphate--diaphorase histochemistry, and staining was quantified with image analysis. Immunohistochemistry was used for the identification of specific nitric oxide synthase isoforms, and immunomarkers were used for the identification of associated cell types.Results: Nitric oxide synthase content was higher in no-touch vessels as compared with conventionally harvested vessels (35.5%; P <.05, with analysis of variance). This content was associated with endothelial nitric oxide synthase on the lumen while all three isoforms were present in the media. In the intact adventitia of no-touch vessels, all three isoforms of nitric oxide synthase were also present, associated with microvessels and perivascular nerves. Perivascular tissue stripping and venous distension both contribute to the reduced nitric oxide synthase in conventionally harvested veins.Conclusion: The new no-touch technique of saphenous vein harvesting preserves nitric oxide synthase, which suggests that improved nitric oxide availability may be an important mechanism in the success of this technique.
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| 8. |
- Tisell, L E, et al.
(författare)
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The Ki67 index a prognostic marker in medullary thyroid carcinoma.
- 2003
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:11, s. 2093-7
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Tidskriftsartikel (refereegranskat)abstract
- Our objective was to examine the usefulness of the Ki67 proliferation index as a prognostic marker in patients with medullary thyroid carcinoma (MTC). It is difficult to predict the prognosis of MTC by using conventional prognostic factors. Immunocytochemical analysis of tumour proliferation has been used as a prognostic tool in some tumours, but only rarely in MTC. In all, 71 tumours from 36 patients were investigated, by using a semiautomatic image analysis programme. On average 10,000 nuclear profiles were counted per tumour, and the percentage of tumour cells expressing the proliferation marker, Ki67, was calculated. Primary tumours that had metastasised had higher Ki67 indices than primary tumours that had not metastasised. Recurrent lymph node metastasis had higher Ki67 indices than the primary tumours. By using a Poisson model, it was possible to estimate the median survival time for individual patients if the Ki67 index for the primary tumour and the age at surgery were known. The higher the Ki67 index and the age at operation were, the shorter was the survival. Estimating the median survival of individual patients will be of help for planning the patients' life and postoperative follow-up and treatment.
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| 9. |
- Asp, Julia, 1973, et al.
(författare)
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Changes in p14(ARF) do not play a primary role in human chondrosarcoma tissues.
- 2001
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Ingår i: International journal of cancer. Journal international du cancer. - 0020-7136. ; 93:5, s. 703-5
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Tidskriftsartikel (refereegranskat)abstract
- The locus encoding the tumor suppressor p16 has been found to code for a second, different protein. This protein, p14(ARF), has been shown to protect p53 from degradation. Like p16, its gene is often altered in different cancers. In this study, the first unique exon, exon 1 beta, of p14(ARF), has been studied in 22 chondrosarcoma tissues using polymerase chain reaction, DNA sequencing and methylation-specific polymerase chain reaction. One chondrosarcoma was found to have exon 1 beta homozygously deleted, but neither mutations nor methylations were found in any of the chondrosarcomas. This indicates that genetic changes of p14(ARF) are a rare event in chondrosarcoma.
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| 10. |
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