| 1. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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| 2. |
- Hasslöf, Pamela, 1978-, et al.
(författare)
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Early intervention with probiotic Lactobacillus paracasei F19 has no long-term effect on caries experience
- 2013
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Ingår i: Caries Research. - : Karger. - 0008-6568 .- 1421-976X. ; 47:6, s. 559-565
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to evaluate possible long-term effects of a cereal diet supplemented with Lactobacillus paracasei F19 (LF19) during weaning on caries experience, mutans streptococci (MS) and lactobacilli (LBC) in a group of 9-year-old children. A secondary aim was to evaluate if the intervention resulted in the permanent integration of LF19 as part of the oral microbiota. The study followed up on a double-blind placebo-controlled randomised trial. Among 179 infants that were randomised to a daily diet that included cereals with or without LF19 from 4 to 13 months of age, 56 from the probiotic group and 62 from the placebo group participated in the follow-up at 9 years. Data were collected by oral clinical examination and questionnaires. MS and LBC levels were assessed with conventional cultivation; LF19 was detected by using randomly amplified polymerase chain reactions (RAPD-PCR). At the follow-up, neither decayed, missing and filled surfaces for primary teeth (dmfs) nor decayed, missing and filled surfaces for permanent teeth (DMFS) differed significantly between the probiotic and placebo groups (p > 0.05). MS and LBC levels were similar in both groups (p > 0.05). RAPD-PCR showed no evidence of oral colonisation with LF19 in the study group. It is concluded that an early intervention with LF19 did not affect the frequency of dental caries, MS or LBC. LF19 did not establish itself as a permanent facet of the oral microbiota in any of the subjects included in this study.
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| 3. |
- Karlsson, Christina, et al.
(författare)
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Effects of long-term storage on the detection of proteins, DNA, and mRNA in tissue microarray slides
- 2011
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Ingår i: Journal of Histochemistry and Cytochemistry. - : Sage Publications. - 0022-1554 .- 1551-5044. ; 59:12, s. 1113-1121
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Tidskriftsartikel (refereegranskat)abstract
- Storage of tissue slides has been claimed to induce dramatically reduced antigen detection particularly for immunohistochemistry (IHC). With tissue microarrays, the necessity to serially cut blocks in order to obtain as much material as possible is obvious. The presumed adverse effect of storage might hamper such an approach. The authors designed an experimental setting consisting of four different storage conditions with storage time of tissue slides of up to 1 year. Detection of proteins, DNA, and mRNA was performed using IHC and in situ hybridization techniques. Slight but significant changes in IHC occurred over time. The most important factor is the primary antibody used: four showed no significant changes, whereas limited decreases in 8 antibodies could be detected by image analysis. Whether the antigen was nuclear or cytoplasmic/membranous did not matter. No major differences between different storage conditions could be shown, but storage at 4C was overall the best procedure. Furthermore, gene copy number aberrations, chromosomal translocations, and the presence of mRNA could be detected on slides stored up to 1 year. In conclusion, in tissues optimally formalin fixed and using modern histological techniques, only minute changes in tissue antigenicity are induced by long-term storage.
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| 4. |
- Karlsson, Christina, 1968-, et al.
(författare)
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Oestrogen receptor ss in NSCLC : prevalence, proliferative influence, prognostic impact and smoking
- 2012
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Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS). - Malden, USA : Wiley-Blackwell. - 0903-4641 .- 1600-0463. ; 120:6, s. 451-458
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Tidskriftsartikel (refereegranskat)abstract
- In non-small-cell lung carcinoma (NSCLC) there are gender differences. The female gender is associated with more adenocarcinomas (ADCA), among both smokers and non-smokers compared to men. Women with NSCLC have a better prognosis compared to men, regardless of other factors. A possible role for oestrogen receptor (ER) signalling has been proposed. The role for ER beta in NSCLC is still not clear, especially concerning the impact of smoking. In a material of NSCLC (n = 262), ER beta and cyclins A1 and A2 were studied by immunohistochemistry on formalin-fixed paraffin embedded tissue. In 137 of those cases, frozen material was available, on which expression analysis of ESR2 (ER beta) and cyclin A1 were performed. Data were correlated to histology, gender, smoking habits, stage and clinical outcome. ER beta was expressed in 86% of the cases. ER beta was most frequently expressed in Stage I ADCAs, especially in male subjects. A correlation between ER beta expression and cyclins was observed in ADCA, also with a male predominance. ER beta transcripts had a positive prognostic impact in ADCA. ER beta transcripts were increased in NSCLC among smokers compared to non-smokers. In conclusion, our data support a role for ER beta in lung ADCAs, proposing a role for ER beta in lungcarcinogenesis, especially among smokers.
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| 5. |
- Karlsson, Margareta, 1958-, et al.
(författare)
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Community nurses' experiences of ethical problems in end-of-life care in the patient's own home.
- 2013
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 0283-9318 .- 1471-6712. ; 27:4, s. 831-838
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To gain a deeper understanding of community nurses' experiences of ethical problems in end-of-life care in the patient's own home. METHOD: Ten female nurses from five different communities with experience of end-of-life care were interviewed. A hermeneutic approach inspired by Gadamer was used to analyse the qualitative data from the interviews. FINDINGS: In the first step of interpretation, two themes emerged: Uncomfortable feelings and Lack of cooperation and in the second step, one theme Lack of security emerged. Finally, the overall interpretation revealed the theme Feelings of loss of control in end-of-life care in the patient's own home. CONCLUSION: The nurses exhibited commitment and a desire to do good when caring for patients in the end-of-life phase, even if they sometimes experienced feelings of lack of control. This implies that, when confronted with care-related issues, they have the power to both act and react. This study aimed to increase understanding of ethical problems that arise in end-of-life care in the patient's own home and revealed the need to take the patients', relatives' and nurses' perspectives on health and suffering into consideration to ensure good end-of-life home care.
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| 6. |
- Stjernström, Annika, et al.
(författare)
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Alterations of INPP4B, PIK3CA and pAkt of the PI3K pathway are associated with squamous cell carcinoma of the lung
- 2014
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Ingår i: Cancer Medicine. - : John Wiley & Sons. - 2045-7634. ; 3:2, s. 337-348
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to investigate how alterations in the PI3K pathway correlate with non-small cell lung cancer subtypes squamous cell carcinoma (SSC) and adenocarcinoma (ADCA). We analyzed copy number variation and protein expression of INPP4B, protein expression of pAkt, PDPK1, and PTEN and mutational status of PIK3CA and PTEN in 180 cases. Nineteen% displayed loss of INPP4B copy, whereas 47% lacked expression, both showing correlation with SCC. Elevated pAkt expression was seen in 63% of all cases, also correlating to SCC. PDPK1 was expressed in 70%, more in male than female patients. Regarding PTEN, 50% displayed loss of expression, of which seven were identified with mutations in the phosphatase domain. We detected nine cases (5%) of PIK3CA mutations, all identified as the E545K hot spot mutation in the helical domain, all except one in SCC. When analyzing all PI3K pathway components together, we show that patients with at least one alteration in the PI3K pathway are twice as likely to have SCC, than ADCA. Interestingly, we also found a strong correlation between high pAkt expression and PTEN expression. As comparison, we also analyzed mitogen-activated protein kinase (MAPK) pathway genes, where we identified fifteen KRAS mutations (8%) and one BRAF mutation (1%), significantly associated to ADCA. No association was found to the Gly972Arg polymorphism of IRS-1, involved in activation of both PI3K and MAPK pathways. In conclusion, we show here that several components of the PI3K pathway, alone and in combination, are correlated to development of SCC of the lung.
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| 7. |
- Barlow, Lotti, et al.
(författare)
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Nationellt fackspråk för vård och omsorg : Slutrapport
- 2011
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Rapport (populärvet., debatt m.m.)abstract
- SammanfattningEtt tillgängligt och använt nationellt fackspråk ska bidra till en god och säker vård och omsorg. Det ska även medverka till att kvaliteten och resultaten på området ska kunna följas upp och jämföras på ett mer effektivt sätt. Slutrapporten presenterar resultatet av projektet Nationellt fackspråk för vård och omsorg samt förslag till förvaltning och utveckling.ResultatetResultatet innefattar bland annat att det internationella begreppssystemet Snomed CT är översatt till svenska och att det är förberett för förvaltning och distribution. Socialstyrelsen har även tagit fram och testat metoder för förvaltning och utveckling av det nationella fackspråket i sin helhet. Därtill har representanter för målgrupperna informerats och fått kunskap.Rapporten innehåller en utförlig beskrivning av det nationella fackspråkets sammantagna innehåll: Socialstyrelsens termbank, klassifikationer och kodverk, den svenska versionen av Snomed CT, metoder för utveckling och förvaltning samt regler för användning.Förvaltning, införande och resursbehovI rapporten finns förslag till hur hela det nationella fackspråket kan tas omhand av Socialstyrelsen och hur det kan införas i vården och omsorgen. Projektets övergång till en långsiktigt hållbar organisation kräver resurser. Därför redogör rapporten för det förväntade resursbehovet för förvaltning och utveckling. Bland annat föreslås en treårig utbildningsinsats samt stimulansbidrag för införande.Krav på styrning, samordning och förtydligat ansvarRapporten betonar behovet av en samlad och medveten styrning av utvecklingen inom området. Socialstyrelsen vill ha en samordnande roll i utvecklingen och förvaltningen av det nationella fackspråket. Myndigheten föreslås få det initiala ansvaret för att utbilda användare och att driva frågor om det nationella fackspråket.Vidare vill Socialstyrelsen få ett uttalat mandat att samordna de nationella aktiviteter som drivs med koppling till Snomed CT. Rapporten pekar ut några särskilt prioriterade områden som myndigheten borde få i uppdrag att arbeta vidare inom.Kunskapsstyrning och normgivningEn viktig slutsats i rapporten är att användningen av det nationella fackspråket behöver regleras för att målet om ökad säkerhet för klienter och patienter ska kunna uppnås. I dagsläget bedöms föreskrifter vara den metod som bäst kan garantera ett brett genomförande.Målgrupper för slutrapportenSlutrapporten riktar sig till beslutsfattare i kommuner och landsting, vård- och omsorgspersonal med särskilt intresse eller ansvar för dokumentationsfrågor och professionella organisationer. Den riktar sig också till terminologiansvariga i kommuner och landsting, IT-direktörer, IT-leverantörer samt aktörer inom den nationella strategin för eHälsa.
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| 8. |
- Bendrik, Christina, et al.
(författare)
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Increased endostatin generation and decreased angiogenesis via MMP-9 by tamoxifen in hormone dependent ovarian cancer
- 2010
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Ingår i: CANCER LETTERS. - : Elsevier Science B.V., Amsterdam.. - 0304-3835. ; 292:1, s. 32-40
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Tidskriftsartikel (refereegranskat)abstract
- There are several similarities between breast and ovarian cancer but anti-estrogen treatment is rarely used in ovarian cancer. We have previously shown that the most widely used anti-estrogen tamoxifen increased MMP-9 activity and endostatin generation in breast cancer. Here, we show that tamoxifen exposure of highly hormone responsive ovarian cancer cells decreased proliferation, and increased MMP-9 activity leading to increased levels of endostatin both in cell culture in vitro and in solid tumors of nude mice. Tamoxifen exposed tumors also exhibited significantly decreased tumor growth and vascularisation. Moreover, in ascites from ovarian cancer patients, MMP-9 was undetectable in majority of cases but a significant correlation of MMP-2 and endostatin was found. The effects on MMPs and endostatin generation are previously unknown mechanisms of estradiol and tamoxifen in ovarian cancer, which may have therapeutic implications in future anti-cancer options of hormone dependent ovarian cancer.
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| 9. |
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| 10. |
- Björnström-Karlsson, Karin, et al.
(författare)
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Orexin A Inhibits Propofol-Induced Neurite Retraction by a Phospholipase D/Protein Kinase C-epsilon-Dependent Mechanism in Neurons
- 2014
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 9:5, s. e0097129-
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Tidskriftsartikel (refereegranskat)abstract
- Background: The intravenous anaesthetic propofol retracts neurites and reverses the transport of vesicles in rat cortical neurons. Orexin A (OA) is an endogenous neuropeptide regulating wakefulness and may counterbalance anaesthesia. We aim to investigate if OA interacts with anaesthetics by inhibition of the propofol-induced neurite retraction. Methods: In primary cortical cell cultures from newborn rats brains, live cell light microscopy was used to measure neurite retraction after propofol (2 mu M) treatment with or without OA (10 nM) application. The intracellular signalling involved was tested using a protein kinase C (PKC) activator [phorbol 12-myristate 13-acetate (PMA)] and inhibitors of Rho-kinase (HA-1077), phospholipase D (PLD) [5-fluoro-2-indolyl des-chlorohalopemide (FIPI)], PKC (staurosporine), and a PKC epsilon translocation inhibitor peptide. Changes in PKC epsilon Ser(729) phosphorylation were detected with Western blot. Results: The neurite retraction induced by propofol is blocked by Rho-kinase and PMA. OA blocks neurite retraction induced by propofol, and this inhibitory effect could be prevented by FIPI, staurosporine and PKC epsilon translocation inhibitor peptide. OA increases via PLD and propofol decreases PKC epsilon Ser(729) phosphorylation, a crucial step in the activation of PKC epsilon. Conclusions: Rho-kinase is essential for propofol-induced neurite retraction in cortical neuronal cells. Activation of PKC inhibits neurite retraction caused by propofol. OA blocks propofol-induced neurite retraction by a PLD/PKC epsilon-mediated pathway, and PKC epsilon maybe the key enzyme where the wakefulness and anaesthesia signal pathways converge.
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