Specific detection of OCT3/4 isoform A/B/B1 expression in solid (germ cell) tumours and cell lines: confirmation of OCT3/4 specificity for germ cell tumours

BACKGROUND: OCT3/4 (POU5F1) is an established diagnostic immunohistochemical marker for specific histological variants of human malignant germ cell tumours (GCTs), including the seminomatous types and the stem cell component of non-seminomas, known as embryonal carcinoma. OCT3/4 is crucial for the regulation of pluripotency and the self-renewal of normal embryonic stem-and germ cells. Detection of expression of this transcription factor is complicated by the existence of multiple pseudogenes and isoforms. Various claims have been made about OCT3/4 expression in non-GCTs, possibly related to using nonspecific detection methods. False-positive findings undermine the applicability of OCT3/4 as a specific diagnostic tool in a clinical setting. In addition, false-positive findings could result in misinterpretation of pluripotency regulation in solid somatic cancers and their stem cells. Of the three identified isoforms - OCT4A, OCT4B and OCT4B1 - only OCT4A proved to regulate pluripotency. Up until now, no convincing nuclear OCT4A protein expression has been shown in somatic cancers or tissues. METHODS: This study investigates expression of the various OCT3/4 isoforms in GCTs (both differentiated and undifferentiated) and somatic (non-germ cell) cancers, including representative cell lines and xenografts. RESULTS: Using specific methods, OCT4A and OCT4B1 are shown to be preferentially expressed in undifferentiated GCTs. The OCT4B variant shows no difference in expression between GCTs (either differentiated or undifferentiated) and somatic cancers. In spite of the presence of OCT4A mRNA in somatic cancer-derived cell lines, no OCT3/4 protein is detected. Significant positive correlations between all isoforms of OCT3/4 were identified in both tumours with and without a known stem cell component, possibly indicating synergistic roles of these isoforms. CONCLUSION: This study confirms that OCT4A protein only appears in seminomatous GCTs, embryonal carcinoma and representative cell lines. Furthermore, it emphasises that in order to correctly assess the presence of functional OCT3/4, both isoform specific mRNA and protein detection are required. British Journal of Cancer (2011) 105, 854-863. doi: 10.1038/bjc.2011.270 www.bjcancer.com Published online 16 August 2011 (C) 2011 Cancer Research U

HG/VNO-label Ondernemen: een stappenplan

Het stappenplan kan worden gebruikt om zicht te krijgen op de omvang en kwaliteit van de ontwikkeling en verankering van ondernemerschapsgericht onderwijs in een opleiding. Daarnaast biedt het instrumentarium om het onderwijs gericht op ondernemen waar nodig of wenselijk te versterken en input om het HG/VNO-NCW MKB Noord - kortweg HG/VNO-label Ondernemen - voor opleidingen en minoren aan te vragen. Dit label levert een externe validering op die bij de werving van studenten en externe communicatie gebruikt kan worden

The Spinal Curvature of Three Different Sitting Positions Analysed in an Open MRI Scanner

Sitting is the most frequently performed posture of everyday life. Biomechanical interactions with office chairs have therefore a long-term effect on our musculoskeletal system and ultimately on our health and wellbeing. This paper highlights the kinematic effect of office chairs on the spinal column and its single segments. Novel chair concepts with multiple degrees of freedom provide enhanced spinal mobility. The angular changes of the spinal column in the sagittal plane in three different sitting positions (forward inclined, reclined, and upright) for six healthy subjects (aged 23 to 45 years) were determined using an open magnetic resonance imaging (MRI) scanner. An MRI-compatible and commercially available office chair was adapted for use in the scanner. The midpoint coordinates of the vertebral bodies, the wedge angles of the intervertebral discs, and the lumbar lordotic angle were analysed. The mean lordotic angles were 16.0±8.5∘ (mean ± standard deviation) in a forward inclined position, 24.7±8.3∘ in an upright position, and 28.7±8.1∘ in a reclined position. All segments from T10-T11 to L5-S1 were involved in movement during positional changes, whereas the range of motion in the lower lumbar segments was increased in comparison to the upper segments