Increased expression of EphA7 correlates with adverse outcome in primary and recurrent glioblastoma multiforme patients

<p>Abstract</p> <p>Background</p> <p>Malignant gliomas are lethal cancers, highly dependent on angiogenesis and treatment options and prognosis still remain poor for patients with recurrent glioblastoma multiforme (GBM). Ephs and ephrins have many well-defined functions during embryonic development of central nervous system such as axon mapping, neural crest cell migration, hindbrain segmentation and synapse formation as well as physiological and abnormal angiogenesis. Accumulating evidence indicates that Eph and ephrins are frequently overexpressed in different tumor types including GBM. However, their role in tumorigenesis remains controversial, as both tumor growth promoter and suppressor potential have been ascribed to Eph and ephrins while the function of EphA7 in GBM pathogenesis remains largely unknown.</p> <p>Methods</p> <p>In this study, we investigated the immunohistochemical expression of EphA7 in a series of 32 primary and recurrent GBM and correlated it with clinical pathological parameters and patient outcome. In addition, intratumor microvascular density (MVD) was quantified by immunostaining for endothelial cell marker von Willebrand factor (vWF).</p> <p>Results</p> <p>Overexpression of EphA7 protein was predictive of the adverse outcome in GBM patients, independent of MVD expression (p = 0.02). Moreover, high density of MVD as well as higher EphA7 expression predicted the disease outcome more accurately than EphA7 variable alone (p = 0.01). There was no correlation between MVD and overall survival or recurrence-free survival (p > 0.05). However, a statistically significant correlation between lower MVD and tumor recurrence was observed (p = 0.003).</p> <p>Conclusion</p> <p>The immunohistochemical assessment of tissue EphA7 provides important prognostic information in GBM and would justify its use as surrogate marker to screen patients for tyrosine kinase inhibitor therapy.</p

EphA2-receptor deficiency exacerbates myocardial infarction and reduces survival in hyperglycemic mice

Background We have previously shown that EphrinA1/EphA expression profile changes in response to myocardial infarction (MI), exogenous EphrinA1-Fc administration following MI positively influences wound healing, and that deletion of the EphA2 Receptor (EphA2-R) exacerbates injury and remodeling. To determine whether or not ephrinA1-Fc would be of therapeutic value in the hyperglycemic infarcted heart, it is critical to evaluate how ephrinA1/EphA signaling changes in the hyperglycemic myocardium in response to MI. Methods Streptozotocin (STZ)-induced hyperglycemia in wild type (WT) and EphA2-receptor mutant (EphA2-R-M) mice was initiated by an intraperitoneal injection of STZ (150 mg/kg) 10 days before surgery. MI was induced by permanent ligation of the left anterior descending coronary artery and analyses were performed at 4 days post-MI. ANOVAs with Student-Newman Keuls multiple comparison post-hoc analysis illustrated which groups were significantly different, with significance of at least p < 0.05. Results Both WT and EphA2-R-M mice responded adversely to STZ, but only hyperglycemic EphA2-R-M mice had lower ejection fraction (EF) and fractional shortening (FS). At 4 days post-MI, we observed greater post-MI mortality in EphA2-R-M mice compared with WT and this was greater still in the EphA2-R-M hyperglycemic mice. Although infarct size was greater in hyperglycemic WT mice vs normoglycemic mice, there was no difference between hyperglycemic EphA2-R-M mice and normoglycemic EphA2-R-M mice. The hypertrophic response that normally occurs in viable myocardium remote to the infarct was noticeably absent in epicardial cardiomyocytes and cardiac dysfunction worsened in hyperglycemic EphA2-R-M hearts post-MI. The characteristic interstitial fibrotic response in the compensating myocardium remote to the infarct also did not occur in hyperglycemic EphA2-R-M mouse hearts to the same extent as that observed in the hyperglycemic WT mouse hearts. Differences in neutrophil and pan-leukocyte infiltration and serum cytokines implicate EphA2-R in modulation of injury and the differences in ephrinA1 and EphA6-R expression in governing this are discussed. Conclusions We conclude that EphA2-mutant mice are more prone to hyperglycemia-induced increased injury, decreased survival, and worsened LV remodeling due to impaired wound healing

Systemic Analysis of Gene Expression Profiles Identifies ErbB3 as a Potential Drug Target in Pediatric Alveolar Rhabdomyosarcoma

Peer reviewe

Discovery in flux: informing design for experience of exploratory walking in changing urban landscapes

Contemporary European cities have been undergoing rapid spatial and social transition (United Nations 2014). Increasingly complex urban environments have been posing challenges to wayfinding — a process of negotiating and moving around unknown quarters (Lynch 1960). Wayshowing — an information design discipline (Per Mollerup 2005) — provides systematic approaches eg directional signage to assist wayfinding. This practice-based and processled research set out to inform future frameworks for wayshowing responsive to urban change. The purpose was not to prevent change, but to reveal productive contrasts in urban transition, (re–)claim and promote city spaces for walking, in the spirit of spatial agency (Awan et al. 2011), enabling social justice and open access. The study focused on exploratory or discursive walkers (Wunderlich 2008) — urban safarians (Demos 2005) — discovering cities for pleasure. This research investigated if, when finding their way in ever fluctuating built and social realms, walkers too were in a state of flux: moving between space (the unknown) and place (the intimate), as in Tuan's a dichotomy of spatial experience (1977: 202): Are space and place the environmental equivalents of the human need for adventure and safety, openness and definition? Discovery in flux: informing design for experience of exploratory walking in changing urban landscapes Abstract A designerly tool based on this question was developed to trigger walkers to undergo a conscious experience in urban loose space: accessible due to temporary lack of top-down control (Franck 2008). During a practice-based study in Hackney Wick (London, 2013–14) nine exploratory walkers experienced wayfinding with the tool. Wayshowing outcomes ie routes and rated photographs, and pre- and post-walking interviews were studied to test whether Tuan’s definition provided cross-walker insight. The results revealed that phenomenologically flâneurian walking combined with conscious reflection on situations was triggered and recorded by the tool. This place-creating tactic (de Certeau 1984) was later represented on an experiential map. Statistically place-like and space-like situations were equally popular but no clear common adventure or safety factors were found. Although cross-walker experience patterns were impossible to define, this study provided insight into: the uniqueness of spatial experience; tools for recording and viewing this experience that brought different results than the interviews (re-telling); and ultimately evidence in critique of systematic wayshowing as a politically neutral, one-size-fits-all solution

Walk ride Camden

An exhibition of work in association with The Socially Responsive Art and Design hub at DACRC looking at ways to inspire those of us who live, visit and work in Camden to walk and cycle more

From Urban Space to Future Place

status: publishe