| 1. |
- Adamovic, Tatjana, 1974, et al.
(författare)
-
Nonrandom pattern of chromosome aberrations in 17beta-estradiol-induced rat mammary tumors: indications of distinct pathways for tumor development.
- 2007
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 46:5, s. 459-69
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogens play an important role in breast cancer etiology and the ACI rat provides a novel animal model for defining the mechanisms through which estrogens contribute to mammary cancer development. In crossing experiments between the susceptible ACI strain and two resistant strains, COP (Copenhagen) and BN (Brown Norway), several quantitative trait loci (QTL) that affect development of 17beta-estradiol (E2)-induced mammary tumors have been defined. Using comparative genomic hybridization (CGH), we have analyzed cytogenetic aberrations in E2-induced mammary cancers and have found clear patterns of nonrandom chromosomal involvement. Approximately two thirds of the tumors exhibited copy number changes. Losses of rat chromosome 5 (RNO5) and RNO20 were particularly common, and it was found that these two aberrations often occurred together. A third recurrent aberration involving proximal gain and distal loss in RNO6 probably defined a distinct subgroup of tumors, since it never occurred in combination with RNO5 loss. Interestingly, QTL with powerful effects on mammary cancer development have been mapped to RNO5 and RNO6. These findings suggest that there were at least two genetic pathways to tumor formation in this rat model of E2-induced mammary cancer. By performing CGH on mammary tumors from ACI rats, F1 rats from crosses between the ACI and COP or BN strains and ACI.BN-Emca8 congenic rats, which carry the BN allele of the Emca8 QTL on RNO5 on the ACI genetic background, we were able to determine that the constitution of the germ line influences the pattern of chromosomal aberrations.
|
|
| 2. |
- Adamovic, Tatjana, 1974, et al.
(författare)
-
Oncogene amplification in the proximal part of chromosome 6 in rat endometrial adenocarcinoma as revealed by combined BAC/PAC FISH, chromosome painting, zoo-FISH, and allelotyping.
- 2005
-
Ingår i: Genes, chromosomes & cancer. - : Wiley. - 1045-2257 .- 1098-2264. ; 44:2, s. 139-53
-
Tidskriftsartikel (refereegranskat)abstract
- The inbred BDII rat is a valuable experimental model for the genetic analysis of endometrial adenocarcinoma (EAC). One common aberration detected by comparative genomic hybridization in rat EAC was gain/amplification affecting the proximal part of rat chromosome 6 (RNO6). We applied rat and mouse chromosome painting probes onto tumor cell metaphase preparations in order to detect and characterize gross RNO6 aberrations. In addition, the RNO6q11-q16 segment was analyzed by fluorescence in situ hybridization with probes representing 12 cancer-related genes in the region. The analysis revealed that seven tumors contained large RNO6-derived homogeneously staining regions (HSRs) in addition to several normal or near-normal RNO6 chromosomes. Five tumors (two of which also had HSRs) exhibited a selective increase of the RNO6q11-q16 segment, sometimes in conjunction with moderate amplification of one or a few genes. Most commonly, the amplification affected the region centered around band 6q16 and included the Mycn, Ddx1, and Rrm2 genes. A second region, centering around Slc8a1 and Xdh, also was affected by gene amplification but to a lesser extent. The aberrations in the proximal part of RNO6 were further analyzed using allelotyping of microsatellite markers in all tumors from animals that were heterozygous in the proximal RNO6 region. We could detect allelic imbalance (AI) in 12 of 20 informative tumors, 6 of which were in addition to those already analyzed by molecular cytogenetic methods as described. Our findings suggest that increase/amplification of genes in this chromosome region contribute to the development of this hormone-dependent tumor.
|
|
| 3. |
|
|
| 4. |
- Behboudi, Afrouz, 1967, et al.
(författare)
-
Detailed chromosomal and radiation hybrid mapping in the proximal part of rat Chromosome 10 and gene order comparison with mouse and human.
- 2002
-
Ingår i: Mammalian genome : official journal of the International Mammalian Genome Society. - : Springer Science and Business Media LLC. - 0938-8990 .- 1432-1777. ; 13:6, s. 302-9
-
Tidskriftsartikel (refereegranskat)abstract
- The rat provides valuable and sometimes unique models of human complex diseases. To fully exploit the rat models in biomedical research, it is important to have access to detailed knowledge of the rat genome organization as well as its relation to the human genome. Rat Chromosome 10 (RNO10) harbors several important cancer-related genes. Deletions in the proximal part of RNO10 were repeatedly found in a rat model for endometrial cancer. To identify functional and positional candidate genes in the affected region, we used radiation hybrid (RH) mapping and single- and dual-color fluorescence in situ hybridization (FISH) techniques to construct a detailed chromosomal map of the proximal part of RNO10. The regional localization of 14 genes, most of them cancer-related ( Grin2a, Gspt1, Crebbp, Gfer, Tsc2, Tpsb1, Il9r, Il4, Irf1, Csf2, Sparc, Tp53, Thra1, Gh1), and of five microsatellite markers ( D10Mit10, D10Rat42, D10Rat50, D10Rat72, and D10Rat165) was determined on RNO10. For a fifteenth gene, Ppm1b, which had previously been assigned to RNO10, the map position was corrected to RNO6q12-q13.
|
|
| 5. |
- Behboudi, Afrouz, 1967, et al.
(författare)
-
The functional significance of absence: the chromosomal segment harboring Tp53 is absent from the T55 rat radiation hybrid mapping panel.
- 2002
-
Ingår i: Genomics. - : Elsevier BV. - 0888-7543 .- 1089-8646. ; 79:6, s. 844-8
-
Tidskriftsartikel (refereegranskat)abstract
- The T55 rat radiation hybrid (RH) mapping panel has been reported to retain the entire rat genome at retention frequencies between 22% and 37%. However, we found that a small segment of rat chromosome 10 harboring at least four different genes, including Tp53, was completely absent from the panel (retention frequency = 0%). Two other markers located in the vicinity exhibited much reduced retention (2-6%). RH clones are generated by transferring highly fragmented DNA into a recipient cell. There might be a strong selection against the transfer and retention of chromosome segments harboring an intact Tp53, as the action of this gene might prevent proliferation and establishment of the RH clone. Our finding further suggests that unexpected low retention or absence of chromosome segments in an RH panel may represent indications that the segments harbor genes with important functions in cell proliferation control.
|
|
| 6. |
- Karlsson, Johanna, 1973, et al.
(författare)
-
Pneumococcal vaccine responses in elderly patients with multiple myeloma, Waldenstrom’s macroglobulinemia, and monoclonal gammopathy of undetermined significance
- 2013
-
Ingår i: Trials in vaccinology. - : Elsevier BV. - 1879-4378. ; 2, s. 31-38
-
Tidskriftsartikel (refereegranskat)abstract
- Background Vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPV) has been recommended for elderly patients with B cell malignancies and dysfunctions because of their enhanced susceptibility to pneumococcal infections. More recent recommendations advocate the use of conjugate pneumococcal vaccines. Methods We compared responses to single dose vaccination with either PPV or the 7-valent pneumococcal conjugate vaccine (PCV7) in fifty-six patients ⩾60 years with a diagnosis of multiple myeloma (n = 24), Waldenstrom’s macroglobulinemia (n = 15) and the non-malignant B cell disorder monoclonal gammopathy of undetermined significance (MGUS) (n = 17), and 20 age-matched controls. Serum was collected prior to vaccination and 4–8 weeks later, and analyzed for IgG antibody levels to pneumococcal serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F by ELISA. Functional antibody activity towards pneumococcal serotypes 4 and 14 was measured using an opsonophagocytic killing assay (OPA). Results All patient groups had lower pre-vaccination IgG antibody and OPA titers to the investigated serotypes compared to the healthy controls. Following vaccination, myeloma patients responded with significant IgG titer increases to 1/7 serotypes and OPA titer increases to 1/2 serotypes. Corresponding IgG and OPA vaccine responses were 3/7 and 0/2 for Waldenstrom patients, 4/7 and 1/2 for MGUS patients, and 4/7 and 2/2 for the healthy controls, respectively. Notably high antibody levels without corresponding OPA titers were seen among a few myeloma patients indicating the presence of non-functional antibodies. Neither of the two vaccines elicited significantly higher serotype-specific IgG concentrations, OPA titers or antibody fold increases in any of the study groups. Hypogammaglobulinemia and ongoing chemotherapy were associated with poor vaccine responses in a multivariate analysis. Conclusion Our findings confirm that B cell malignancies and disorders among elderly patients are associated with suboptimal responses to pneumococcal vaccination. Single-dose PCV7 was not shown to be superior to PPV.
|
|
| 7. |
- Nyman, Viola, 1961, et al.
(författare)
-
Routine interventions in childbirth before and after initiation of an Action Research project : Sexual & Reproductive Healthcare
- 2017
-
Ingår i: Sexual and Reproductive Healthcare. - : Elsevier BV. - 1877-5756 .- 1877-5764. ; 11, s. 86-90
-
Tidskriftsartikel (refereegranskat)abstract
- © 2016 Elsevier B.V.Background Unnecessary routine interventions in uncomplicated labour and birth, like cardiotocography (CTG), amniotomy, use of scalp electrode and oxytocin treatment, are associated with further interventions that could harm the woman and the infant. A four year Action Research (AR) project was done on a labour ward to enhance the capacity of local midwives in the promotion of physiological labour and birth. Aim To describe the use of interventions during labour and birth in healthy women at term with spontaneous onset of labour, before and after initiation of an Action Research project. Methods A retrospective before and after comparative study of clinical records from 2009 (before) and 2012 (after), based on a random selection of records from primiparous and multiparous women. Outcome measures were duration of admission CTG, frequency of admission CTG over 30 min, frequency of amniotomy, use of scalp electrode, and frequency of oxytocin augmentation in spontaneous labour. Results 903 records were included. The duration of admission CTG (p = 0.001), frequency of admission CTG duration over 30 min (p = <0.001), the use of scalp electrodes (p = <0.001), and use of oxytocin augmentation of spontaneous labour (p = 0.014) were reduced significantly after initiation of the AR project. There were no significant differences in frequency of amniotomy, duration of total CTG, postpartum bleeding, sphincter tears, Apgar score <5 at 5 min, and mode of birth. Conclusion Following an AR project, several interventions were reduced during labour and birth. Controlled studies in other settings are needed to assess the impact of collaborative action on decreasing unnecessary interventions.
|
|
| 8. |
|
|
