The role of VEGF and a functional link between VEGF and p27(Kip1) in acute myeloid leukemia.

Alterations in the expression and signalling pathways of vascular endothelial growth factor (VEGF) have been linked to the clinical features and pathogenesis of hematologic malignancies. In this study, we showed that VEGF protein expression was statistically significantly higher in the leukemic blasts than in the normal hematopoietic counterparts. A statistically significant correlation between expression of VEGF and p27(Kip1) was observed in bone marrows from 42 patients with acute myeloid leukemia (P<0.001). We further demonstrated that forced VEGF overexpression or autocrine VEGF stimulation of VEGFR-2 triggers proliferation and migration/invasion of U-937 leukemic cells, thereby inducing a more invasive tumor phenotype. U-937 cells overexpressing VEGF were resistant to all-trans-retinoic acid-(ATRA) or camptothecin-induced apoptosis. Finally, we showed that increased p27(Kip1) expression enhanced the ability of VEGF and VEGFR-2 to promote the migration of U-937 cells. Taken together, our results suggest that elevated level of VEGF may contribute to the adverse patient outcome by promoting cell growth, survival and migration of leukemic cells and by reducing the sensitivity of leukemic cells to therapeutic agents-induced apoptosis.Leukemia advance online publication, 6 November 2008; doi:10.1038/leu.2008.300

Analysis of the growth dynamics of angiogenesis-dependent and -independent experimental glioblastomas by multimodal small-animal PET and MRI

Copyright © 2012 by the Society of Nuclear Medicine, Inc

Tumor versus Stromal Cells in Culture—Survival of the Fittest?

<div><p>Two of the signature genetic events that occur in human gliomas, <i>EGFR</i> amplification and <i>IDH</i> mutation, are poorly represented in experimental models <i>in vitro</i>. <i>EGFR</i> amplification, for example, occurs in 40 to 50% of GBM, and yet, <i>EGFR</i> amplification is rarely preserved in cell cultures derived from human tumors. To analyze the fate of <i>EGFR</i> amplified and <i>IDH</i> mutated cells in culture, we followed the development over time of cultures derived from human xenografts in nude rats enriched for tumor cells with <i>EGFR</i> amplification and of cultures derived from patient samples with <i>IDH</i> mutations, in serum monolayer and spheroid suspension culture, under serum and serum free conditions. We observed under serum monolayer conditions, that nestin positive or nestin and SMA double positive rat stromal cells outgrew <i>EGFR</i> amplified tumor cells, while serum spheroid cultures preserved tumor cells with <i>EGFR</i> amplification. Serum free suspension culture exhibited a more variable cell composition in that the resultant cell populations were either predominantly nestin/SOX2 co-expressing rat stromal cells or human tumor cells, or a mixture of both. The selection for nestin/SMA positive stromal cells under serum monolayer conditions was also consistently observed in human oligodendrogliomas and oligoastrocytomas with <i>IDH</i> mutations. Our results highlight for the first time that serum monolayer conditions can select for stromal cells instead of tumor cells in certain brain tumor subtypes. This result has an important impact on the establishment of new tumor cell cultures from brain tumors and raises the question of the proper conditions for the growth of the tumor cell populations of interest.</p></div

Adopting incentive mechanisms for large-scale participation in mobile crowdsensing: from literature review to a conceptual framework

Mobile crowdsensing is a burgeoning concept that allows smart cities to leverage the sensing power and ubiquitous nature of mobile devices in order to capture and map phenomena of common interest. At the core of any successful mobile crowdsensing application is active user participation, without which the system is of no value in sensing the phenomenon of interest. A major challenge militating against widespread use and adoption of mobile crowdsensing applications is the issue of how to identify the most appropriate incentive mechanism for adequately and efficiently motivating participants. This paper reviews literature on incentive mechanisms for mobile crowdsensing and proposes the concept of SPECTRUM as a guide for inferring the most appropriate type of incentive suited to any given crowdsensing task. Furthermore, the paper highlights research challenges and areas where additional studies related to the different factors outlined in the concept of SPECTRUM are needed to improve citizen participation in mobile crowdsensing. It is envisaged that the broad range of factors covered in SPECTRUM will enable smart cities to efficiently engage citizens in large-scale crowdsensing initiatives. More importantly, the paper is expected to trigger empirical investigations into how various factors as outlined in SPECTRUM can influence the type of incentive mechanism that is considered most appropriate for any given mobile crowdsensing initiative

Rat stromal cells or a combination of tumor and stromal cells have a growth advantage in serum free cultures.

<p><b>(a)</b> FISH with an <i>EGFR</i>/Chromosome 7 probe in red and green, respectively, and immunohistochemical staining with antibodies against EGFR. In P8 cultures, both EGFR amplification and the chromosome 7 probe are not detectable after two months. In P6 cultures, EGFR amplification is preserved in spheroids (dotted line), while both EGFR amplification and the chromosome 7 probe are not detectable in single cells. EGFR expression is lost in P8 cultures, while it is still detectable at a low expression level in spheroids from P6 cultures. Quantification of EGFR expressing cells in three random high power (400×) microscopic view fields (HPF) in each group. Asterix indicates 0%. Values represent mean ± s.d. <b>(b)</b> Immunohistochemical staining with antibodies against human-specific and rat-specific nestin. In P8 cultures, rat-nestin positive stromal cells have a growth advantage over human cells. In P6 cultures, a mix of human and rat cells survive. Human cells form spheroids, while single cells are rat cells. Scale bars 50 µm. Quantification of rat and human nestin expressing cells in three random high power (400×) microscopic view fields (HPF) in each group. Asterix indicates 0%. Values represent mean ± s.d.</p