| 11. |
- Bergdahl, Ingvar A., et al.
(författare)
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Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
- 1997
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Ingår i: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 0901-9928. ; 81:4, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
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| 12. |
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| 13. |
- Nilsson, Henrik, et al.
(författare)
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Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice
- 1997
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 76:3, s. 355-364
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Tidskriftsartikel (refereegranskat)abstract
- The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.
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| 14. |
- Nordén, T, et al.
(författare)
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Mammographic screening for breast cancer : What cancers do we find?
- 1997
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Ingår i: European Journal of Cancer. - : Elsevier. - 0959-8049 .- 1879-0852. ; 33:4, s. 624-628
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to compare lymph node involvement of breast cancer cases detected at mammography screening with clinically-detected cases. During a 3-year period, 273 primary breast cancers were detected in a population-based screening programme, and 149 primary breast cancers were diagnosed clinically. Lymph node involvement was evaluated in univariate and multivariate logistic regression models correcting for tumour size, histological grade, steroid receptor status and DNA-ploidy. Patients with screen-detected cancers had a low relative risk of having lymph node metastases (univariate, OR = 0.31; 95% confidence interval = 0.19-0.52). In the multivariate logistic regression model, the relative risk was halved (OR = 0.47; 0.28-0.78). The reduced risk was more pronounced for women younger than 50 years of age compared to older women. The risk for screen-detected cases of having lymph node metastases at diagnosis was statistically significantly lower than for clinically-detected cases. The marked reduction, even when correcting for tumour size, makes it less likely that factors such as detection of clinically innocent tumours, length bias sampling or clinical symptoms related to axillary metastases can explain the whole difference. The results indicate at least part of the effect may be explained by tumour progression in the late preclinical detectable phase.
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| 15. |
- Nordlund, Lars Anders, et al.
(författare)
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Cancer incidence in female smokers : a 26-year follow-up
- 1997
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Ingår i: International Journal of Cancer. - 0020-7136 .- 1097-0215. ; 73:5, s. 625-628
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Tidskriftsartikel (refereegranskat)abstract
- A random sample of 26,000 Swedish women who were asked about their smoking habits in the early 1960s have now been followed for 26 years with respect to cancer incidence. Most findings regarding tobacco smoking and cancer from studies of men were confirmed also among the women. Elevated relative risk for current smokers compared with women who never smoked regularly were seen for cancers of the lung, upper aerodigestive sites, pancreas, bladder, cervix and all cancers combined, as well as a notably high relative risk for cancers of organs of the urinary tract other than kidney and bladder. Relative risk increased with dose, measured as grams of tobacco smoked per day, for cancers of the upper aerodigestive sites, lung, cervix, bladder, organs of the urinary tract other than kidney and bladder and all cancers combined. For cancers of the lung, bladder and cervix, there was an inverse relationship with age when starting to smoke tobacco. The reported inverse relationship between smoking and endometrial cancer could not be corroborated, nor was there any significant relationship between smoking and colorectal or breast cancer.
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| 16. |
- Hakansson, Sara, et al.
(författare)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 17. |
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| 18. |
- Wängberg, Bo, 1953, et al.
(författare)
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Somatostatin Receptors in the Diagnosis and Therapy of Neuroendocrine Tumor.
- 1997
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Ingår i: The oncologist. - 1549-490X. ; 2:1, s. 50-58
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Tidskriftsartikel (refereegranskat)abstract
- The expression of somatostatin receptors in neuroendocrine tumors has facilitated the diagnosis and surgical treatment of patients with these tumors. After injection of a radiolabeled long-acting somatostatin analog, (111)In-octreotide, scintigraphic tumor imaging can ben performed as well as intraoperative tumor localization. During localization studies very high (111)In concentration values were found in tumor tissues versus normal tissues, especially in carcinoid tumors and endocrine pancreatic tumors. Studies on such tumors in cell culture further indicated internalization of (111)In into tumor cells, which is a prerequisite for a radiobiological effect from short range Auger and conversion electrons. Attempts to systemic radionuclide therapy via somatostatin receptors in patients with neuroendocrine tumors have been initiated.
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| 19. |
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| 20. |
- Ehinger, M, et al.
(författare)
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The tumor suppressor gene p53 can mediate transforming growth [corrected] factor beta1-induced differentiation of leukemic cells independently of activation of the retinoblastoma protein
- 1997
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Ingår i: Cell Growth and Differentiation. - 1044-9523. ; 8:10, s. 37-1127
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Tidskriftsartikel (refereegranskat)abstract
- Although the involvement of the tumor suppressor gene p53 in normal hematopoiesis is uncertain, it can give rise to differentiation signals in leukemic cells. It is not clear, however, whether differentiation merely is a consequence of the ability of p53 to arrest cell proliferation or whether hitherto unknown molecular mechanisms are responsible for the p53-mediated differentiation. To further explore the role of p53 in leukemic cell differentiation, we investigated whether transforming growth factor beta1 (TGF-beta1), a cytokine involved in cell cycle control at several levels, can cooperate with wild-type p53 to induce differentiation of monoblastic U-937 and erythroleukemic K562 cells. Indeed, wild-type p53-expressing cells were found to be more sensitive to TGF-beta1-induced differentiation than control cells, lending support to the idea that p53 is of importance for differentiation induction of leukemic cells. In addition, it is shown that TGF-beta1 can suppress p53-mediated cell death, thus reinforcing the differentiation response. The cyclin-dependent kinase inhibitor p21 and the retinoblastoma protein (pRb) are downstream effectors of p53-mediated growth arrest. Therefore, the roles for these molecules in p53-mediated differentiation were examined. The p53-dependent signals of differentiation were associated with induction of p21 in both cell lines investigated. However, activation of pRb by induced hypophosphorylation and concomitant decreased growth rate on p53-mediated differentiation was observed only in U-937 cells expressing an inducible, temperature-sensitive form of p53 but not in K562 cells constitutively expressing p53. Thus, our data suggest a role for p53 in the regulation of differentiation in leukemic cells that can be independent of its ability to activate pRb and arrest cell proliferation.
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