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- Andersson, Patiyan, 1978-, et al.
(författare)
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Genome-wide analysis of penile cancer using high-density single nucleotide polymorphism arrays
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The availability of genome-wide high-density single nucleotide polymorphism (SNP) arrays makes it possible to in a structured manner study chromosome aberrations in penile cancer where little is known of disruptive genetic events. In this study 19 penile squamous cell carcinomas were analyzed using the 250k NspI SNP array from Affymetrix. We find major regions of frequent copy number gain in chromosome arms 3q, 5p and 8q, and slightly less frequent in 1p, 16q and 20q. The chromosomal regions of most frequent copy number losses were 3p, 4q, 11p and 13q. We identified four candidate genes residing in the major chromosomal regions of aberration. Eight tumours showed copy number gain of the PIK3CA gene located to 3q26.3. Five of the remaining tumours carried an activating mutation of the PIK3CA gene and these tumours showed very few chromosomal aberrations. Collectively, disruption of the PIK3CA gene was found in 13/19 samples, and presence of active phosphorylated AKT was confirmed immunohistochemically in these tumours indicating an active signalling pathway. We found copy number gain of the hTERT gene (5p15.33) in 7 samples and of the Myc gene (8q24.21) in 7 samples. Copy number loss of the tumoursuppressor gene FHIT (3p14.2) was observed in 8 samples, the same 8 samples that showed copy number gain of the PIK3CA gene. In total the PI3K/AKT and RAS/MAPK pathways were found to be activated through mutation or amplification in 64% of the cases, indicating the significance of these pathways in the aetiology of penile cancer.
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| 2. |
- Andersson, Sten-Ove, et al.
(författare)
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Doctors’ and Nurses’ Perceptions of Military Pre-hospital Emergency Care
- 2014
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The aim of this study was to identify physicians’ and nurses’ perceptions of military prehospital emergency care before and after an international mission. A qualitative empirical study with a phenomenographic approach was used. The aim is to identify the area of knowledge, pre-hospital care in a military environment, in terms of expressions from doctors and nurses focussing on the variation in how learning of pre-hospital care is perceived. The result of the study is a set of descriptive categories on a collective level, showing the variation in how doctors and nurses perceived the phenomenon of military pre-hospital emergency care. The results after predeployment training can be categorized as (1) to learn military medicine, (2) to take care of the casualty and (3) to have safety awareness. The results after an international mission can be categorized as (1) to collaborate with others, (2) to deliver general health care, and (3) to improve competence in military medicine. Possible implications of the results from the present study are the following; (I) better conditions for doctors and nurses to provide appropriate military medical care by clarification and better understanding of professions in the mission area (doctors, nurses, officers), since they may have different goals for their actions, (II) to pay attention to all aspects of military health care during predeployment training, including general health care in the mission area, (III) to implement new knowledge in military medicine in the predeployment training, and (IV) to train for the reality all doctors and nurses are about to meet. These results indicate that the training should be developed in order to optimize the prepare physicians and nurses for international assignments. This may result in increased safety for the provider of care, while at the same time minimizing suffering and enhancing the possibility of survival of the injured.
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| 4. |
- Barros Brant Carvalho, Paulo Henrique, et al.
(författare)
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Neutron scattering study of polyamorphic THF ∙ (H2O)17 – toward a generalized picture of amorphous states and structures derived from clathrate hydrates
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- From crystalline tetrahydrofuran clathrate hydrate, THF-CH (THF ∙ 17H2O, cubic structure II), three distinct polyamorphs can be derived. First, THF-CH undergoes pressure-induced amorphization when pressurized to 1.3 GPa in the temperature range 77–140 K to a form which, in analogy to pure ice, may be called high-density amorphous (HDA). Second, HDA can be converted to a densified form, very-HDA (VHDA), upon heat-cycling at 1.8 GPa to 180 K. Decompression of VHDA to atmospheric pressure below 130 K produces the third, recovered amorphous (RA) form. Results from a compilation of neutron scattering experiments and molecular dynamics simulations provide a generalized picture of the structure of amorphous THF hydrates with respect to crystalline THF-CH and liquid THF ∙ 17H2O solution (~2.5 M). The calculated density of (only in situ observable) HDA and VHDA at 2 GPa and 130 K is 1.287 and 1.328 g/cm3, respectively, whereas that of RA (at 1 atm) is 1.081 g/cm3. Although fully amorphous, HDA is heterogeneous with two length scales for water-water correlations (less dense local water structure) and guest-water correlations (denser THF hydration structure). The hydration structure of THF is influenced by guest-host hydrogen bonding. THF molecules maintain a quasiregular array, reminiscent of the crystalline state, and their hydration structure (out to 5 Å) constitutes ~23 H2O. The local water structure in HDA is reminiscent of pure HDA-ice, featuring 5-coordinated H2O. In VHDA, this structure is maintained but the local water structure is densified to resemble pure VHDA-ice with 6-coordinated H2O. The hydration structure of THF in RA constitutes ~18 H2O and the water structure corresponds to a strictly 4-coordinated network, as in the liquid. Both VHDA and RA can be considered as homogeneous, solid solutions of THF and water. The local water structure of water-rich (1:17) amorphous CHs resembles most that of the corresponding amorphous water ices when compared to guest-rich CHs, e.g., Ar ∙ ~6H2O. The proposed significance of different contributions of water local environments presents a simple view to justify neutron structure factor features.
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| 8. |
- Svensson, Maria A., et al.
(författare)
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A comparative study of ERG status assessment on DNA-, mRNA-, and proteinlevels using unique samples from a Swedish biopsy cohort
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The ERG rearrangement is identified in approximately 50% of prostate cancer (PCa) screened cohorts and is known to be highly specific. This genetic aberration, most commonly leading to the TMPRSS2-ERG fusion, but also SLC45A3-ERG or NDRG1- ERG fusions, all leading to an over expression of a truncated ERG protein. Most studies have applied in situ hybridization (FISH) methods or mRNA based assays to investigate the ERG status. Recently, studies showed that ERG protein levels assessed by ERG antibodies can be used as a surrogate marker for ERG rearrangement. In the current study we investigate ERG status on a series of diagnostic biopsies using DNA-, mRNA- and protein based assays. We formally compare three assay results (i.e. FISH, fusion mRNA and immunohistochemistry) to identify which method could be most appropriate to use when having limited amount of tissue. ERG rearrangement was found in 56% of the cases. Comparing ERG rearrangement status by FISH with ERG over expression and TMPRSS2-ERG fusion transcript we found 95.1% (154/162, Fisher’s exact test 9.50E-36) and 85.2% (138/162, Fisher’s exact test 7.26E-22) concordance, respectively. We show that the ERG antibody highly correlates with the ERG rearrangement with high sensitivity and specificity. We also identified the most common TMPRSS2-ERG isoform in the majority of ERG rearranged cases. These results provide compelling evidence that the ERG antibody can be used to further investigate the role of ERG in PCa.
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| 9. |
- Svensson, Maria A., et al.
(författare)
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ERG rearrangement status and castration resistant prostate cancer : a prospective,population-based study
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Overtreatment is a major concern in prostate cancer (PCa) management, as no adequate prognostic tool exists to separate indolent from aggressive disease at time of diagnosis. Androgen deprivation therapy (ADT) is the standard treatment of locally recurrent or metastatic PCa and although most men respond well to ADT initially, inevitably a resistance to the treatment develops. Men with tumor growth despite the androgen-depleted environment are considered to have castration resistant PCa (CRPC). After developing CRPC, the median survival time is typically less than two years. Since the initial discovery of ERG rearrangement in PCa, several studies have investigated the association between ERG rearrangement and clinical outcome of PCa with discrepant results. Few studies have examined the association between ERG rearrangement and CRPC, despite the fact that the most common fusion partners to ERG are androgen regulated. In this study we investigated the association between ERG status and time to CRPC.We assessed the ERG status in a cohort of 220 men initially managed by watchful waiting and treated with ADT at disease progression. There was no statistically significant association between ERG status and time from start of ADT to CPRC, or start of ADT to PCa-specific death. However, men harboring the ERG rearrangement did have a significantly shorter time between time of diagnosis and start of hormonal treatment, compared to men without the rearrangement (HR: 1.81; 95% CI: 1.23- 2.65), suggesting that ERG rearrangement is indicative of a more aggressive subtype of PCa./p>
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