Non-Invasive In Vivo Imaging of Tumor-Associated CD133/Prominin

detection of cancer stem cells is of great importance. detection of CD133/prominin, a cancer stem cell surface marker for a variety of tumor entities. The CD133-specific monoclonal antibody AC133.1 was used for quantitative fluorescence-based optical imaging of mouse xenograft models based on isogenic pairs of CD133 positive and negative cell lines. A first set consisted of wild-type U251 glioblastoma cells, which do not express CD133, and lentivirally transduced CD133-overexpressing U251 cells. A second set made use of HCT116 colon carcinoma cells, which uniformly express CD133 at levels comparable to primary glioblastoma stem cells, and a CD133-negative HCT116 derivative. Not surprisingly, visualization and quantification of CD133 in overexpressing U251 xenografts was successful; more importantly, however, significant differences were also found in matched HCT116 xenograft pairs, despite the lower CD133 expression levels. The binding of i.v.-injected AC133.1 antibodies to CD133 positive, but not negative, tumor cells isolated from xenografts was confirmed by flow cytometry. imaging of tumor-associated CD133 is feasible and that CD133 antibody-based tumor targeting is efficient. This should facilitate developing clinically applicable cancer stem cell imaging methods and CD133 antibody-based therapeutics

Human monoclonal antibodies targeting carbonic anhydrase IX for the molecular imaging of hypoxic regions in solid tumours

BACKGROUND: Hypoxia, which is commonly observed in areas of primary tumours and of metastases, influences response to treatment. However, its characterisation has so far mainly been restricted to the ex vivo analysis of tumour sections using monoclonal antibodies specific to carbonic anhydrase IX (CA IX) or by pimonidazole staining, after the intravenous administration of this 2-nitroimidazole compound in experimental animal models.METHODS: In this study, we describe the generation of high-affinity human monoclonal antibodies (A3 and CC7) specific to human CA IX, using phage technology.RESULTS: These antibodies were able to stain CA IX ex vivo and to target the cognate antigen in vivo. In one of the two animal models of colorectal cancer studied (LS174T), CA IX imaging closely matched pimonidazole staining, with a preferential staining of tumour areas characterised by little vascularity and low perfusion. In contrast, in a second animal model (SW1222), distinct staining patterns were observed for pimonidazole and CA IX targeting. We observed a complementary pattern of tumour regions targeted in vivo by the clinical-stage vascular-targeting antibody L19 and the anti-CA IX antibody A3, indicating that a homogenous pattern of in vivo tumour targeting could be achieved by a combination of the two antibodies.CONCLUSION: The new human anti-CA IX antibodies are expected to be non-immunogenic in patients with cancer and may serve as broadly applicable reagents for the non-invasive imaging of hypoxia and for pharmacodelivery applications. British Journal of Cancer (2009) 101, 645-657. doi: 10.1038/sj.bjc.6605200 www.bjcancer.com Published online 21 July 2009 (C) 2009 Cancer Research U

Stuck between a rock and a hard place: the work situation for nurses as leaders in municipal health care

Etty R Nilsen,1 Anja H Olafsen,1 Anne Grethe Steinsvåg,2 Hallgeir Halvari,1 Ellen K Grov31Department of Strategy and Finance, School of Business, University College of Southeast-Norway, 2Department of Nursing Science, Faculty of Health Sciences, University College of Southeast-Norway, Kongsberg, 3Department of Nursing and Health Promotion, Faculty of Health Sciences, Oslo and Akershus University College, Oslo, NorwayBackground: The paper aims to present how nursing leaders in the municipal health care perceive the interaction with and support from their superiors and peers. The paper further aims to identify the leaders’ vulnerability and strength at work in the current situation of shortage of manpower and other resources in the health care sector. This is seen through the lens of self-determination theory.Methods: Qualitative interviews were conducted with nine nursing leaders in nursing homes and home-care services, which, in part, capture the municipal health care service in a time of reform.Results: The nursing leaders are highly independent regarding their role as leaders. They act with strength and power in their position as superiors for their own staff, but they lack support and feel left alone by their leader, the municipal health director. The relation between the nursing leaders and their superiors is characterized by controlling structures and lack of autonomy support. As a consequence, the nursing leaders’ relations with subordinates and particularly peers, contribute to satisfy their needs for competence and relatedness, and, to some extent, autonomy. However, this cannot substitute for the lack of support from the superior level.Conclusion: The paper maintains a need to increase the consciousness of the value of horizontal support and interaction with peers and subordinates for the municipal nursing leader. Also, the need for increased focus on “the missing link” upward between the municipal health director and the nursing leader is revealed. The impact of extensive controlling structures and lack of autonomy support from superiors might lead to reduced motivation and well-being.Keywords: motivation, nursing leader, leadership, municipal health care servic