Barn som vekker bekymring: barnehagelæreres bekymring for barns omsorgssituasjon

Alle barn har det ikke bra hjemme. Jeg har minner fra egen barndom hvor jeg som barn opplevde at enkelte barn hadde det annerledes hjemme enn oss andre barna. Som barn fikk jeg inntrykk av at alle visste om det, også voksne. Det var synd på disse barna husker jeg at jeg opplevde som en feller tanke. Det gjorde inntrykk på meg som barn, og har fulgt meg siden. Jeg har gjennom hele studietiden ved barnehagelærerutdanningen hatt et ekstra engasjement for temaet barn i risiko, og endte med å velge bekymring for barns omsorgssituasjon som tema for min bacheloroppgave. Barn har rett til omsorg og beskyttelse, beskyttelse mot svikt i omsorgen og alle former for vold og overgrep står det nedfelt i barnekonvensjonen forankret i menneskerettighetene (FNs konvensjon om barns rettigheter, artikkel 3, 2003). Barnehagen skal bygge på verdigrunnlaget fastsatt i barnehageloven og internasjonale konvensjoner Norge har sluttet seg til, slik som barnekonvensjonen. Dette verdigrunnlaget skal gjenspeiles i barnehagens daglige arbeid og aktiviteter, barnehagen skal møte barns individuelle behov for omsorg, trygghet og tilhørighet, samt fremme livsmestring, likestilling og helse (Kunnskapsdepartementet, 2017, s.10). I vårt samfunn går omtrent alle barn mellom 1-5 år i barnehagen. Tall fra statistisk sentralbyrå viser at pr. 13.mars 2020 går 92,2% av alle barn i alderen 1-5 år i barnehage i Norge (SSB, 2020). Barnehageansatte er i daglig kontakt med barn og familier, jobber tett sammen med foreldrene om den daglige omsorgen for barnet og har dermed en unik mulighet til å oppdage og avverge omsorgssvikt. Min problemstilling er følgende: «Hvilke erfaringer har barnehagelærere med barn som vekker bekymring?»publishedVersionBNBAC390

Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a Human GBM Xenograft Model

Object. Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12Gy or 18Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls ( < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls ( < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment ( = 0.04). Conclusion.GKS administered with clinically relevant doses prolongs survival in rats harboringGBMxenografts, and the associated toxicity is mild.publishedVersio

Tumour-associated glial host cells display a stem-like phenotype with a distinct gene expression profile and promote growth of GBM xenografts

Background: Little is known about the role of glial host cells in brain tumours. However, supporting stromal cells have been shown to foster tumour growth in other cancers. Methods: We isolated stromal cells from patient-derived glioblastoma (GBM) xenografts established in GFP-NOD/scid mice. With simultaneous removal of CD11b+ immune and CD31+ endothelial cells by fluorescence activated cell sorting (FACS), we obtained a population of tumour-associated glial cells, TAGs, expressing markers of terminally differentiaed glial cell types or glial progenitors. This cell population was subsequently characterised using gene expression analyses and immunocytochemistry. Furthermore, sphere formation was assessed in vitro and their glioma growth-promoting ability was examined in vivo. Finally, the expression of TAG related markers was validated in human GBMs. Results: TAGs were highly enriched for the expression of glial cell proteins including GFAP and myelin basic protein (MBP), and immature markers such as Nestin and O4. A fraction of TAGs displayed sphere formation in stem cell medium. Moreover, TAGs promoted brain tumour growth in vivo when co-implanted with glioma cells, compared to implanting only glioma cells, or glioma cells and unconditioned glial cells from mice without tumours. Genome-wide microarray analysis of TAGs showed an expression profile distinct from glial cells from healthy mice brains. Notably, TAGs upregulated genes associated with immature cell types and self-renewal, including Pou3f2 and Sox2. In addition, TAGs from highly angiogenic tumours showed upregulation of angiogenic factors, including Vegf and Angiopoietin 2. Immunohistochemistry of three GBMs, two patient biopsies and one GBM xenograft, confirmed that the expression of these genes was mainly confined to TAGs in the tumour bed. Furthermore, their expression profiles displayed a significant overlap with gene clusters defining prognostic subclasses of human GBMs. Conclusions: Our data demonstrate that glial host cells in brain tumours are functionally distinct from glial cells of healthy mice brains. Furthermore, TAGs display a gene expression profile with enrichment for genes related to stem cells, immature cell types and developmental processes. Future studies are needed to delineate the biological mechanisms regulating the brain tumour-host interplay.publishedVersio

Neuronal markers are expressed in human gliomas and NSE knockdown sensitizes glioblastoma cells to radiotherapy and temozolomide

<p>Abstract</p> <p>Background</p> <p>Expression of neuronal elements has been identified in various glial tumors, and glioblastomas (GBMs) with neuronal differentiation patterns have reportedly been associated with longer survival. However, the neuronal class III β-tubulin has been linked to increasing malignancy in astrocytomas. Thus, the significance of neuronal markers in gliomas is not established.</p> <p>Methods</p> <p>The expressions of class III β-tubulin, neurofilament protein (NFP), microtubule-associated protein 2 (MAP2) and neuron-specific enolase (NSE) were investigated in five GBM cell lines and two GBM biopsies with immunocytochemistry and Western blot. Moreover, the expression levels were quantified by real-time qPCR under different culture conditions. Following NSE siRNA treatment we used Electric cell-substrate impedance sensing (ECIS) to monitor cell growth and migration and MTS assays to study viability after irradiation and temozolomide treatment. Finally, we quantitated NSE expression in a series of human glioma biopsies with immunohistochemistry using a morphometry software, and collected survival data for the corresponding patients. The biopsies were then grouped according to expression in two halves which were compared by survival analysis.</p> <p>Results</p> <p>Immunocytochemistry and Western blotting showed that all markers except NFP were expressed both in GBM cell lines and biopsies. Notably, qPCR demonstrated that NSE was upregulated in cellular stress conditions, such as serum-starvation and hypoxia, while we found no uniform pattern for the other markers. NSE knockdown reduced the migration of glioma cells, sensitized them to hypoxia, radio- and chemotherapy. Furthermore, we found that GBM patients in the group with the highest NSE expression lived significantly shorter than patients in the low-expression group.</p> <p>Conclusions</p> <p>Neuronal markers are aberrantly expressed in human GBMs, and NSE is consistently upregulated in different cellular stress conditions. Knockdown of NSE reduces the migration of GBM cells and sensitizes them to hypoxia, radiotherapy and chemotherapy. In addition, GBM patients with high NSE expression had significantly shorter survival than patients with low NSE expression. Collectively, these data suggest a role for NSE in the adaption to cellular stress, such as during treatment.</p

Barn som vekker bekymring: barnehagelæreres bekymring for barns omsorgssituasjon

Alle barn har det ikke bra hjemme. Jeg har minner fra egen barndom hvor jeg som barn opplevde at enkelte barn hadde det annerledes hjemme enn oss andre barna. Som barn fikk jeg inntrykk av at alle visste om det, også voksne. Det var synd på disse barna husker jeg at jeg opplevde som en feller tanke. Det gjorde inntrykk på meg som barn, og har fulgt meg siden. Jeg har gjennom hele studietiden ved barnehagelærerutdanningen hatt et ekstra engasjement for temaet barn i risiko, og endte med å velge bekymring for barns omsorgssituasjon som tema for min bacheloroppgave. Barn har rett til omsorg og beskyttelse, beskyttelse mot svikt i omsorgen og alle former for vold og overgrep står det nedfelt i barnekonvensjonen forankret i menneskerettighetene (FNs konvensjon om barns rettigheter, artikkel 3, 2003). Barnehagen skal bygge på verdigrunnlaget fastsatt i barnehageloven og internasjonale konvensjoner Norge har sluttet seg til, slik som barnekonvensjonen. Dette verdigrunnlaget skal gjenspeiles i barnehagens daglige arbeid og aktiviteter, barnehagen skal møte barns individuelle behov for omsorg, trygghet og tilhørighet, samt fremme livsmestring, likestilling og helse (Kunnskapsdepartementet, 2017, s.10). I vårt samfunn går omtrent alle barn mellom 1-5 år i barnehagen. Tall fra statistisk sentralbyrå viser at pr. 13.mars 2020 går 92,2% av alle barn i alderen 1-5 år i barnehage i Norge (SSB, 2020). Barnehageansatte er i daglig kontakt med barn og familier, jobber tett sammen med foreldrene om den daglige omsorgen for barnet og har dermed en unik mulighet til å oppdage og avverge omsorgssvikt. Min problemstilling er følgende: «Hvilke erfaringer har barnehagelærere med barn som vekker bekymring?

Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

Background The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. Methods 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O2, à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. Results The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. Conclusions The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway. An anti-angiogenic effect after intermittent HBO was observed, and reflected in the gene expression profile

Gamma knife surgery as monotherapy with clinically relevant doses prolongs survival in a Human GBM Xenograft Model

Object. Gamma knife surgery (GKS) may be used for recurring glioblastomas (GBMs). However, patients have then usually undergone multimodal treatment, which makes it difficult to specifically validate GKS independent of established treatments. Thus, we developed an experimental brain tumor model to assess the efficacy and radiotoxicity associated with GKS. Methods. GBM xenografts were implanted intracerebrally in nude rats, and engraftment was confirmed with MRI. The rats were allocated to GKS, with margin doses of 12Gy or 18Gy, or to no treatment. Survival time was recorded, tumor sections were examined, and radiotoxicity was evaluated in a behavioral open field test. Results. In the first series, survival from the time of implantation was 96 days in treated rats and 72 days in controls ( < 0.001). In a second experiment, survival was 72 days in the treatment group versus 54 days in controls ( < 0.006). Polynuclear macrophages and fibrosis was seen in groups subjected to GKS. Untreated rats with GBM xenografts displayed less mobility than GKS-treated animals in the open field test 4 weeks after treatment ( = 0.04). Conclusion.GKS administered with clinically relevant doses prolongs survival in rats harboringGBMxenografts, and the associated toxicity is mild

Gene expression in tumor cells and stroma in dsRed 4T1 tumors in eGFP-expressing mice with and without enhanced oxygenation

Abstract Background The tumor microenvironment is pivotal in tumor progression. Thus, we aimed to develop a mammary tumor model to elucidate molecular characteristics in the stroma versus the tumor cell compartment by global gene expression. Secondly, since tumor hypoxia influences several aspects of tumor pathophysiology, we hypothesized that hyperoxia might have an inhibitory effect on tumor growth per se. Finally, we aimed to identify differences in gene expression and key molecular mechanisms, both in the native state and following treatment. Methods 4T1 dsRed breast cancer cells were injected into eGFP expressing NOD/SCID mice. Group 1 was exposed to 3 intermittent HBO treatments (Day 1, 4 and 7), Group 2 to 7 daily HBO treatments (both 2.5bar, 100% O2, à 90 min), whereas the controls were exposed to a normal atmosphere. Tumor growth, histology, vascularisation, cell proliferation, cell death and metastasis were assessed. Fluorescence-activated cell sorting was used to separate tumor cells from stromal cells prior to gene expression analysis. Results The purity of sorted cells was verified by fluorescence microscopy. Gene expression profiling demonstrated that highly expressed genes in the untreated tumor stroma included constituents of the extracellular matrix and matrix metalloproteinases. Tumor growth was significantly inhibited by HBO, and the MAPK pathway was found to be significantly reduced. Immunohistochemistry indicated a significantly reduced microvessel density after intermittent HBO, whereas daily HBO did not show a similar effect. The anti-angiogenic response was reflected in the expression trends of angiogenic factors. Conclusions The present in vivo mammary tumor model enabled us to separate tumor and stromal cells, and demonstrated that the two compartments are characterized by distinct gene expressions, both in the native state and following HBO treatments. Furthermore, hyperoxia induced a significant tumor growth-inhibitory effect, with significant down-regulation of the MAPK pathway. An anti-angiogenic effect after intermittent HBO was observed, and reflected in the gene expression profile.</p