| 1. |
- Bergman, Annika, et al.
(författare)
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Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families : Suggestive linkage to 10q23.32-q25.3
- 2007
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Ingår i: Genes, Chromosomes and Cancer. - : John Wiley & Sons. - 1045-2257 .- 1098-2264. ; 46:3, s. 302-309
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Tidskriftsartikel (refereegranskat)abstract
- The two breast cancer genes BRCA1 and BRCA2 were identified more than 10 years ago and, depending on population, mutations in these genes are responsible for a varying percentage of familial breast cancer. In more than half the families, the increased risk of breast cancer cannot be explained by mutations in these genes, and the goal of this study was to locate novel susceptibility genes. One of the main difficulties in identifying the cause of hereditary non-BRCA1/BRCA2 breast cancer is genetic heterogeneity, possibly due to multiple, incompletely penetrant susceptibility genes, along with ethnic and geographic differences. In this study, one large family and 13 small to medium-sized families with multiple cases of breast cancer were analyzed by genome-wide linkage analysis. The genome scan was performed by genotype analysis of 10,000 SNP markers on microarrays. The strongest evidence of linkage (HLOD 2.34) was obtained on chromosome region 10q23.32-q25.3. A further two regions were identified, with LOD scores above 2.10 on 12q14-q21 and 19p13.3-q12. In a subset of families of western Swedish origin, two regions generated LOD scores exceeding 1.8: 10q23.32-q25.3 and 19q13.12-q13.32. The large family in the study exceeded LOD 1.5 in three regions: 10q23.32-q25.3, 19q13.12-q13.32, and 17p13. Our results indicate that one or more of the suggested regions may harbor genes that are involved in the development of breast cancer.
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| 2. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
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Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')2: therapeutic efficacy and myelotoxicity
- 2006
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Ingår i: Nucl Med Biol. - : Elsevier BV. - 0969-8051. ; 33:8, s. 1065-72
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. METHODS: Animals were intraperitoneally inoculated with approximately 1x10(7) cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with approximately 800, 3x approximately 267, approximately 400, 3x approximately 133, approximately 50 or 3x approximately 17 kBq (211)At-MX35 F(ab')(2) (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab')(2) (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the (211)At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the (211)At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the alpha-particles emitted by (211)At in the bone marrow. RESULTS: The tumor-free fractions of animals were 56% and 41% when treated with approximately 800 kBq and 3x approximately 267 kBq (211)At-MX35 F(ab')(2), respectively; 39% and 28% when treated with approximately 400 kBq and 3x approximately 133 kBq (211)At-MX35 F(ab')(2), respectively; and 17% and 22% when treated with approximately 50 kBq or 3x approximately 17 kBq (211)At-MX35 F(ab')(2), respectively. The nadir of the white blood cell (WBC) counts was decreased (from 46% to 19%, compared with the baseline WBC counts) and delayed (from Day 4 to Day 11 after the first injection) during the fractionated treatment compared with the single-dose treatment. The percentage of injected activity per gram (%IA/g) for blood, bone and bone marrow all peaked 6 h after injection at 13.80+/-1.34%IA/g, 4.00+/-0.69%IA/g and 8.28+/-1.38%IA/g, respectively. The BBLR and BMBLR were 0.20+/-0.04 and 0.58+/-0.01, respectively. The mean absorbed dose to bone marrow was approximately 0.4 Gy after intraperitoneally injecting approximately 800 kBq (211)At-MX35 F(ab')(2). CONCLUSION: No advantage was observed in the therapeutic efficacy of using a fractionated regimen compared with a single administration, with the same total amount of administered activity. Alleviation of the myelotoxicity was observed during the fractionated regimen in terms of decreased suppression and delayed nadir of the WBC counts. No thrombocytopenia was observed during either regimen.
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| 3. |
- Kenne Sarenmalm, Elisabeth, 1956, et al.
(författare)
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Changes in health-related quality of life may predict recurrent breast cancer.
- 2009
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Ingår i: European Journal of Oncology Nursing. - : Elsevier BV. - 1532-2122 .- 1462-3889. ; 13:5, s. 323-329
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patient-reported outcomes incorporated in cancer clinical trials, are increasingly hypothesized to be predictors of disease-free survival. Previous research supports health-related quality of life (HRQoL) as an independent predictor of survival in patients with advanced or metastatic breast cancer. In contrast, recent studies provide evidence that baseline HRQoL scores are not associated with increased risk of relapse or survival in women with early-stage breast cancer. One plausible assumption might be that baseline HRQoL scores are limited as predictors of a recurrence of breast cancer several years after the initial diagnosis. In this explorative study, we examined whether changes in HRQoL over time may predict breast cancer recurrence. As a supplement, we investigated whether baseline HRQoL predicted recurrence. METHODS: The study sample consisted of 141 participants in the International Breast Cancer Study Group adjuvant Trial 12-93 and Trial 14-93, from the Western region of Sweden. HRQoL was assessed, during a 5-year follow up. Poisson regression analysis was used to estimate the hazard function of recurrence depending on time since primary diagnosis and on HRQoL variables. RESULTS: According to the Poisson multivariable regression analysis changes in physical well-being (beta=0.00439, p-value=0.0470), and nausea/vomiting (beta=-0.00612, p-value=0.0136) significantly predicted recurrence. Baseline HRQoL outcomes were not predictors of recurrence. CONCLUSIONS: Changes of HRQoL during adjuvant therapy may be associated with recurrence. This explorative finding needs prospective investigation.
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| 4. |
- Skarnemark, Gunnar, 1948, et al.
(författare)
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Production of Rh-103m for cancer therapy
- 2009
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Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 280:2, s. 371-373
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Tidskriftsartikel (refereegranskat)
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| 5. |
- Bergman, Annika, et al.
(författare)
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No germline mutations in supposed tumour suppressor genes SAFB1 and SAFB2 in familial breast cancer with linkage to 19p.
- 2008
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Ingår i: BMC Medical Genetics. - : BioMed Central. - 1471-2350. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The scaffold attachment factor B1 and B2 genes, SAFB1/SAFB2 (both located on chromosome 19p13.3) have recently been suggested as tumour suppressor genes involved in breast cancer development. The assumption was based on functional properties of the two genes and loss of heterozygosity of intragenic markers in breast tumours further strengthened the postulated hypothesis. In addition, linkage studies in Swedish breast cancer families also indicate the presence of a susceptibility gene for breast cancer at the 19p locus. Somatic mutations in SAFB1/SAFB2 have been detected in breast tumours, but to our knowledge no studies on germline mutations have been reported. In this study we investigated the possible involvement of SAFB1/SAFB2 on familiar breast cancer by inherited mutations in either of the two genes.RESULTS: Mutation analysis in families showing linkage to the SAFB1/2 locus was performed by DNA sequencing. The complete coding sequence of the two genes SAFB1 and SAFB2 was analyzed in germline DNA from 31 affected women. No missense or frameshift mutations were detected. One polymorphism was found in SAFB1 and eight polymorphisms were detected in SAFB2. MLPA-anlysis showed that both alleles of the two genes were preserved which excludes gene inactivation by large deletions.CONCLUSION: SAFB1 and SAFB2 are not likely to be causative of the hereditary breast cancer syndrome in west Swedish breast cancer families.
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