The Intracellular Localization of ID2 Expression Has a Predictive Value in Non Small Cell Lung Cancer

ID2 is a member of a subclass of transcription regulators belonging to the general bHLH (basic-helix-loophelix) family of transcription factors. In normal cells, ID2 is responsible for regulating the balance between proliferation and differentiation. More recent studies have demonstrated that ID2 is involved in tumor progression in several cancer types such as prostate or breast

Id-1 and Id-2 are markers for metastasis and prognosis in oesophageal squamous cell carcinoma

Id protein family consists of four members namely Id-1 to Id-4. Different from other basic helix–loop–helix transcription factors, they lack the DNA binding domain. Id proteins have been shown to be dysregulated in many different cancer types and their prognostic value has also been demonstrated. Recently, Id-1 has been shown to be upregulated in oesophageal squamous cell carcinoma (ESCC). However, the prognostic implications of Id proteins in ESCC have not been reported. We examined the expression of the Id proteins in ESCC cell lines and clinical ESCC specimens and found that Id protein expressions were dysregulated in both the ESCC cell lines and specimens. By correlating the expression levels of Id proteins and the clinicopathological data of our patient cohort, we found that M1 stage tumours had significantly higher nuclear Id-1 expression (P=0.012) while high nuclear Id-1 expression could predict development of distant metastasis within 1 year of oesophagectomy (P=0.005). In addition, high levels of Id-2 expression in both cytoplasmic and nuclear regions predicted longer patient survival (P=0.041). Multivariate analysis showed that high-level expression of Id-2 in both cytoplasmic and nuclear regions and lower level of nuclear Id-1 expression were independent favourable predictors of survival in our ESCC patients. Our results suggest that Id-1 may promote distant metastasis in ESCC, and both Id-1 and Id-2 may be used for prognostication for ESCC patients

SSeCKS/Gravin/AKAP12 attenuates expression of proliferative and angiogenic genes during suppression of v-Src-induced oncogenesis

BACKGROUND: SSeCKS is a major protein kinase C substrate with kinase scaffolding and metastasis-suppressor activity whose expression is severely downregulated in Src- and Ras-transformed fibroblast and epithelial cells and in human prostate, breast, and gastric cancers. We previously used NIH3T3 cells with tetracycline-regulated SSeCKS expression plus a temperature-sensitive v-Src allele to show that SSeCKS re-expression inhibited parameters of v-Src-induced oncogenic growth without attenuating in vivo Src kinase activity. METHODS: We use cDNA microarrays and semi-quantitative RT-PCR analysis to identify changes in gene expression correlating with i) SSeCKS expression in the absence of v-Src activity, ii) activation of v-Src activity alone, and iii) SSeCKS re-expression in the presence of active v-Src. RESULTS: SSeCKS re-expression resulted in the attenuation of critical Src-induced proliferative and pro-angiogenic gene expression including Afp, Hif-1α, Cdc20a and Pdgfr-β, and conversely, SSeCKS induced several cell cycle regulatory genes such as Ptpn11, Gadd45a, Ptplad1, Cdkn2d (p19), and Rbbp7. CONCLUSION: Our data provide further evidence that SSeCKS can suppress Src-induced oncogenesis by modulating gene expression downstream of Src kinase activity

Cyclin E overexpression and associated events in human breast cancer

Unrestrained proliferation is a hallmark of cancer and genetic defects within G1/S-phase regulation and the pRb pathway occur frequently. Proliferation control can be circumvented either by excess cyclin D1 or cyclin E, alterations that can define two alternative tumour biologic pathways in breast cancer. By overexpressing cyclin E in a cell line model system we demonstrate that the capacity of cells to normalize the level of active cyclin E/cdk2 was dependent on the ability to upregulate and re-direct p21 and p27 to the active kinase complex, as could be observed in ER positive and cyclin D1 high, but not the ER negative and cyclin E high cell lines. The results further indicated that cyclin E and associated kinase activities might regulate proliferation independent of pRb. One alternative substrate for cyclin E kinase is the ID2 protein. Upon ID2 overexpression, the proliferative capacity increased but the invasive potential of breast cancer cell lines decreased. In primary breast cancer, high ID2 expression was associated with a favourable outcome and a less aggressive and more differentiated luminal breast cancer phenotype. Next we evaluated the incidence of aberrant cyclin E expression in the S/G2/M-phases, and investigated the potential tumour biologic characteristics associated with impaired cyclin E degradation. Cyclin E overexpressing breast cancer cells lines displayed varying ability to degrade excess cyclin E, and exhibited prolonged S-phase progression. Tumours with aberrant cell cycle specific expression pattern of cyclin E correlated inversely with survival status of patients and there was a favour for c-myc amplification within this group of tumours. We further characterised potential novel functions of cyclin E, and breast cancer cell lines overexpressing cyclin E induced significant changes in gene expression related to cell adhesion. Cells further showed an impaired capacity to migrate and invade through ECM. In primary breast cancer we observed a positive correlation between cyclin E expression and tumours with a pushing growth pattern and a medullary breast cancer type, clearly validating the cell line observations. Due to the link between cyclin E and growth pattern, as well as survival, cyclin E expression was consequently associated with impaired prognosis exclusively in patients with breast cancer with an infiltrative growth pattern. Thus, the effects of cyclin E expression and breast cancer progression are multiple, including altered proliferation as well as tumour growth pattern

Extra anpassningar i grundskolan : - Belastning, svårighet eller en möjlighet?

År 2014 kom en ny lag gällande arbetet med extra anpassningar. I lagen tydliggörs den undervisande pedagogens skyldighet att sätta in extra anpassningar i ett skede där eleven inte ses nå målen. Ändringen i skollagen har medfört direkta och indirekta effekter på arbetet med extra anpassningar inom skolor i Sverige. Utifrån ramfaktorteorin såsom den skrivs fram av Dahllöf och Skritics teori om byråkratiska och adhocratiska organisationer var syftet med studien att undersöka olika professioners syn på arbetet kring extra anpassningar inom skolan som organisation. Utifrån en fenomenologisk kvalitativ intervjustudie med åtta deltagare fick vi några rektorers, lärares, speciallärares och specialpedagogers samt specialpedagogstudenters syn på fenomenet extra anpassningar sett utifrån den egna professionen. Resultaten tolkades mot bakgrund av Skrtics teori om att specialpedagogiska system kan uppstå inom skolan som organisation trots skollagens intention om inkluderande och tillgängliga lärmiljöer för alla elever inom skolan. Resultaten visade att medvetenheten och kännedomen om extra anpassningar som begrepp och fenomen kändes till av samtliga deltagare och att lagändringen år 2014 påverkade deltagarnas syn på sitt arbete med extra anpassningar. Deltagarnas olika syn på att organisera och leda arbetet med extra anpassningar tydde på att lagändringen tolkades olika beroende på profession och skola

Women's experiences of recovery after myocardial infarction and unstable angina

Hjärtinfarkt och instabil angina ingår i de sjukdomar som ökar mest bland kvinnor runt om i världen. Återhämtning är en viktig del av tillfrisknandet och innebär att personen kämpar för att återgå till livet innan sjukdomen och återfå sina tidigare funktioner. Syftet med denna litteraturstudie var att beskriva kvinnors upplevelser av återhämtning efter hjärtinfarkt och instabil angina. I litteraturstudien ingick nio vetenskapliga artiklar. Dessa analyserades med en kvalitativ innehållsanalys med induktiv ansats för att få en djupare förståelse av upplevelser. Analysen resulterade i fyra kategorier: att begränsas i sitt dagliga liv, att dela erfarenheter med andra innebar stöd, att eftertrakta normalitet och information, att ta ansvar och bli självständig.   Resultatet visade att kvinnor hade behov av stöd från andra och att vårdpersonal utgjorde en viktig del i deras återhämtningsprocess. Författarna anser att vidare forskning om kvinnors återhämtning kan vara värdefull för vårdpersonal för att bli medvetna om behov och kunna anpassa sitt bemötande för att uppnå en mer jämlik vård.

Women's experiences of recovery after myocardial infarction and unstable angina

Hjärtinfarkt och instabil angina ingår i de sjukdomar som ökar mest bland kvinnor runt om i världen. Återhämtning är en viktig del av tillfrisknandet och innebär att personen kämpar för att återgå till livet innan sjukdomen och återfå sina tidigare funktioner. Syftet med denna litteraturstudie var att beskriva kvinnors upplevelser av återhämtning efter hjärtinfarkt och instabil angina. I litteraturstudien ingick nio vetenskapliga artiklar. Dessa analyserades med en kvalitativ innehållsanalys med induktiv ansats för att få en djupare förståelse av upplevelser. Analysen resulterade i fyra kategorier: att begränsas i sitt dagliga liv, att dela erfarenheter med andra innebar stöd, att eftertrakta normalitet och information, att ta ansvar och bli självständig.   Resultatet visade att kvinnor hade behov av stöd från andra och att vårdpersonal utgjorde en viktig del i deras återhämtningsprocess. Författarna anser att vidare forskning om kvinnors återhämtning kan vara värdefull för vårdpersonal för att bli medvetna om behov och kunna anpassa sitt bemötande för att uppnå en mer jämlik vård.

High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells

ID proteins have been implicated in the regulation of cell proliferation and differentiation in various cell types during normal development as well as in the formation of cancer. Our aim was to delineate the expression of ID2 by immunohistochemistry in primary breast cancer in order to detect potential associations with cell cycle regulatory proteins and/or clinicopathologic parameters. We further overexpressed ID2 in a breast cancer cell line to elaborate potential effects on proliferation and invasiveness. We observed large variations in ID2 expression in primary breast cancer, and the protein was localised to both the nucleus and cytoplasm. Interestingly, a high cytoplasmic ID2 protein level correlated with a favourable prognosis. Overexpressing ID2 in the MDA-MB-468 breast cancer cell line generated a marked cytoplasmic localisation of the protein and reduced the invasive capacity of cells. Modest enhancement of cell proliferation was further detected in ID2-overexpressing cells. In conclusion, ID2 protein expression varies substantially within primary breast tumours and high cytoplasmic levels of ID2 might reflect a less aggressive breast tumour phenotype