Identification of proteins involved in neural progenitor cell targeting of gliomas

<p>Abstract</p> <p>Background</p> <p>Glioblastoma are highly aggressive tumors with an average survival time of 12 months with currently available treatment. We have previously shown that specific embryonic neural progenitor cells (NPC) have the potential to target glioma growth in the CNS of rats. The neural progenitor cell treatment can cure approximately 40% of the animals with malignant gliomas with no trace of a tumor burden 6 months after finishing the experiment. Furthermore, the NPCs have been shown to respond to signals from the tumor environment resulting in specific migration towards the tumor. Based on these results we wanted to investigate what factors could influence the growth and progression of gliomas in our rodent model.</p> <p>Methods</p> <p>Using microarrays we screened for candidate genes involved in the functional mechanism of tumor inhibition by comparing glioma cell lines to neural progenitor cells with or without anti-tumor activity. The expression of candidate genes was confirmed at RNA level by quantitative RT-PCR and at the protein level by Western blots and immunocytochemistry. Moreover, we have developed <it>in vitro </it>assays to mimic the antitumor effect seen <it>in vivo</it>.</p> <p>Results</p> <p>We identified several targets involved in glioma growth and migration, specifically CXCL1, CD81, TPT1, Gas6 and AXL proteins. We further showed that follistatin secretion from the NPC has the potential to decrease tumor proliferation. <it>In vitro </it>co-cultures of NPC and tumor cells resulted in the inhibition of tumor growth. The addition of antibodies against proteins selected by gene and protein expression analysis either increased or decreased the proliferation rate of the glioma cell lines <it>in vitro</it>.</p> <p>Conclusion</p> <p>These results suggest that these identified factors might be useful starting points for performing future experiments directed towards a potential therapy against malignant gliomas.</p

Early Developing Pig Embryos Mediate Their Own Environment in the Maternal Tract

The maternal tract plays a critical role in the success of early embryonic development providing an optimal environment for establishment and maintenance of pregnancy. Preparation of this environment requires an intimate dialogue between the embryo and her mother. However, many intriguing aspects remain unknown in this unique communication system. To advance our understanding of the process by which a blastocyst is accepted by the endometrium and better address the clinical challenges of infertility and pregnancy failure, it is imperative to decipher this complex molecular dialogue. The objective of the present work is to define the local response of the maternal tract towards the embryo during the earliest stages of pregnancy. We used a novel in vivo experimental model that eliminated genetic variability and individual differences, followed by Affymetrix microarray to identify the signals involved in this embryo-maternal dialogue. Using laparoscopic insemination one oviduct of a sow was inseminated with spermatozoa and the contralateral oviduct was injected with diluent. This model allowed us to obtain samples from the oviduct and the tip of the uterine horn containing either embryos or oocytes from the same sow. Microarray analysis showed that most of the transcripts differentially expressed were down-regulated in the uterine horn in response to blastocysts when compared to oocytes. Many of the transcripts altered in response to the embryo in the uterine horn were related to the immune system. We used an in silico mathematical model to demonstrate the role of the embryo as a modulator of the immune system. This model revealed that relatively modest changes induced by the presence of the embryo could modulate the maternal immune response. These findings suggested that the presence of the embryo might regulate the immune system in the maternal tract to allow the refractory uterus to tolerate the embryo and support its development

Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Dynamic IPS²-Networks and -Operations Based on Software Agents

Organised by: Cranfield UniversityThis article describes how an IPS² network should be build up by considering the dynamic behavior of the IPS² along its life-cycle. How the network partner could participate and how they allocate their capacities will be also discussed as questions regarding the commissioning by considering the business model. The realization of this concept is based on a multi-agent system. Therefore all service delivery involved IPS² objects like product, network partner and service technicians are represented by software agents. All this will be pointed out by an availability oriented maintenance scenario in the field of micro production.Mori Seiki – The Machine Tool Compan

Esposizione: WALTER A. NOEBEL. PROJEKTIONEN, Ravenna, Urban Center, 2 febbraio - 2 marzo 2008

L'esposizione dal titolo "Walter A. Noebel. Projektionen", curata da Valter Balducci e Helmut Geisert, \ue8 presentata a Ravenna presso l'Urban Center, nella sede espositiva della chiesa di San Domenico, dal 2 febbraio al 2 marzo 2008. L\u2019evento presentato costituisce l\u2019edizione rinnovata dell\u2019esposizione presentata nell'aprile 2007 a Cesena nella chiesa dello Spirito Santo. La mostra presenta l\u2019opera di Walter A. Noebel, uno dei pi\uf9 singolari interpreti della contemporanea cultura architettonica tedesca, berlinese in particolare, attraverso un\u2019attenta selezione di progetti e costruzioni che coprono il ventennio dagli anni Ottanta ad oggi. La vasta sintesi presentata offre un ampio spaccato della sua vasta produzione architettonica, permettendo di individuare i principali temi del suo originale percorso intellettuale, lontano dalle contemporanee oscillazioni del gusto ma fortemente radicato nella cultura della modernit\ue0. I molti disegni presentati nelle numerose tavole e nei 6 modelli illustrano 45 progetti svolti dalla fine degli anni Ottanta ad oggi. La mostra, curata da Valter Balducci per la Facolt\ue0 di Architettura \u201cAldo Rossi\u201d, sar\ue0 successivamente aperta anche nella citt\ue0 di Napoli. Alla mostra si accompagna un catalogo omonimo, edito dalla CLUEB di Bologna

Walter A. Noebel. Projektionen. Esperimenti di adeguatezza e coerenza

L'esposizione dal titolo "Walter A. Noebel. Projektionen. Esperimenti di adeguatezza e coerenza", curata da Valter Balducci e Helmut Geisert, è stata presentata a Cesena nello spazio espositivo della chiesa dello Spirito Santo dal 2 al 30 aprile 2007. La mostra, attraverso un’attenta selezione di opere, offre un ampio spaccato della vasta produzione architettonica di un singolare interprete della contemporanea cultura architettonica tedesca, berlinese in particolare. Essa ha l’ambizione di individuare i temi caratteristici del suo originale percorso intellettuale, lontano dalle contemporanee oscillazioni del gusto ma fortemente radicato nella cultura della modernità. Attraverso i molti disegni presentati in 45 tavole, i 6 modelli e le 16 fotografie di grande formato, saranno illustrati 45 progetti svolti dalla fine degli anni Ottanta ad oggi. . La mostra, curata da Valter Balducci per la Facoltà di Architettura “Aldo Rossi”, sarà successivamente aperta anche nelle città di Ravenna e di Napoli. Alla mostra si accompagna un catalogo dallo stesso titolo, edito dalla CLUEB di Bologna