Assessment of Epidermal Growth Factor Receptor (EGFR) expression in human meningioma

<p>Abstract</p> <p>Purpose</p> <p>This study explores whether meningioma expresses epidermal growth factor receptor (EGFR) and determines if there is a correlation between the WHO grade of this tumor and the degree of EGFR expression.</p> <p>Methods</p> <p>Following institutional review board approval, 113 meningioma specimens from 89 patients were chosen. Of these, 85 were used for final analysis. After a blinded review, immunohistochemical stains for EGFR were performed. Staining intensity (SI) was scored on a scale 0-3 (from no staining to strong staining). Staining percentage of immunoreactive cells (SP) was scored 1-5 (from the least to the maximum percent of the specimen staining). Immunohistochemical score (IHS) was calculated as the product of SI and SP.</p> <p>Results</p> <p>Eighty-five samples of meningioma were classified in accordance with World Health Organization (WHO) criteria: benign 57/85 (67%), atypical 23/85 (27%), and malignant 5/85 (6%). The majority of samples demonstrated a moderate SI for EGFR. IHS for EGFR demonstrated a significant association between SI and histopathologic subtype. Also, there was a correlation between the SP and histopathologic subtype (p = 0.029). A significant association was determined when the benign and the atypical samples were compared to the malignant with respect to the SP (p = 0.009). While there was a range of the IHS for the benign and the atypical histologic subtypes, malignant tumors exhibited the lowest score and were statistically different from the benign and the atypical specimens (p < 0.001).</p> <p>Conclusions</p> <p>To our knowledge, this represents the largest series of meningioma samples analyzed for EGFR expression reported in the literature. EGFR expression is greatest in benign meningiomas and may serve a potential target for therapeutic intervention with selective EGFR inhibitors.</p

The Cooperation between hMena Overexpression and HER2 Signalling in Breast Cancer

hMena and the epithelial specific isoform hMena11a are actin cytoskeleton regulatory proteins belonging to the Ena/VASP family. EGF treatment of breast cancer cell lines upregulates hMena/hMena11a expression and phosphorylates hMena11a, suggesting cross-talk between the ErbB receptor family and hMena/hMena11a in breast cancer. The aim of this study was to determine whether the hMena/hMena11a overexpression cooperates with HER-2 signalling, thereby affecting the HER2 mitogenic activity in breast cancer. In a cohort of breast cancer tissue samples a significant correlation among hMena, HER2 overexpression, the proliferation index (high Ki67), and phosphorylated MAPK and AKT was found and among the molecular subtypes the highest frequency of hMena overexpressing tumors was found in the HER2 subtype. From a clinical viewpoint, concomitant overexpression of HER2 and hMena identifies a subgroup of breast cancer patients showing the worst prognosis, indicating that hMena overexpression adds prognostic information to HER2 overexpressing tumors. To identify a functional link between HER2 and hMena, we show here that HER2 transfection in MCF7 cells increased hMena/hMena11a expression and hMena11a phosphorylation. On the other hand, hMena/hMena11a knock-down reduced HER3, AKT and p44/42 MAPK phosphorylation and inhibited the EGF and NRG1-dependent HER2 phosphorylation and cell proliferation. Of functional significance, hMena/hMena11a knock-down reduced the mitogenic activity of EGF and NRG1. Collectively these data provide new insights into the relevance of hMena and hMena11a as downstream effectors of the ErbB receptor family which may represent a novel prognostic indicator in breast cancer progression, helping to stratify patients

SPARC 2017 retrospect & prospects : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2017 SPARC conference. This year we not only celebrate the work of our PGRs but also the 50th anniversary of Salford as a University, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 130 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to exploit this great opportunity to engage with researchers working in different subject areas to your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

SPARC 2018 Internationalisation and collaboration : Salford postgraduate annual research conference book of abstracts

Welcome to the Book of Abstracts for the 2018 SPARC conference. This year we not only celebrate the work of our PGRs but also the launch of our Doctoral School, which makes this year’s conference extra special. Once again we have received a tremendous contribution from our postgraduate research community; with over 100 presenters, the conference truly showcases a vibrant PGR community at Salford. These abstracts provide a taster of the research strengths of their works, and provide delegates with a reference point for networking and initiating critical debate. With such wide-ranging topics being showcased, we encourage you to take up this great opportunity to engage with researchers working in different subject areas from your own. To meet global challenges, high impact research inevitably requires interdisciplinary collaboration. This is recognised by all major research funders. Therefore engaging with the work of others and forging collaborations across subject areas is an essential skill for the next generation of researchers

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

Functional Outcome in the Neurosurgical Patient and Its Impact on Quality of Life

Outcomes research has become an integral part of most clinical studies today. Extent of resection, increased median survival, and “time to progression” are no longer the only important end points in need of assessment. Identifying the long-term adverse effects of treatment has become increasingly important as patients try to resume previous activities and an independent lifestyle. The measurement of functional states and health-related quality of life issues are at the forefront of medicine and have become necessary measures of functional outcome following the treatment of a variety of medical and surgical disorders. In this article, we review the most recent studies on the functional outcome of patients undergoing neurological surgeries and its impact on quality of life