Alternatives to Hydrofluoric Acid Etching At Wyman Gordon Company

The goal of this project was to explore alternatives to the use of hydrofluoric acid in the removal of alpha case from the surface of forged titanium for the Wyman-Gordon Company. Both fluoroboric acid and a solution of sodium fluoride and ammonium persulfate were experimentally tested. Results showed that hydrofluoric acid had the highest etch rate over 6 minutes. Recommendations for future research were made to improve the current process. &#8195

Assessment of Energy Reduction Campaign: An Analysis of the Behavioral and Attitudinal Impacts of an Environmental Initiative in the Danish Municipality of Lyngby-Taarbaek

This report, prepared for The Science Shop, reviews the impact of an energy reduction campaign upon the attitudes of city employees in the Danish municipality of Lyngby-Taarbaek. This assessment was accomplished through the analysis of energy consumption records from five different municipal buildings, interviews with key informants and information gathered through an internet survey. The campaign had a significant impact upon the attitudes of many municipal employees, although this did not result in energy savings in all cases

Glioblastoma formation in a recurrent intracranial epidermoid cyst: a case report

Background: Transformation to glioblastoma following recurrent epidermoid cyst resection has not been reported. Chronic inflammation can underlie malignant transformation of epidermoid cysts. Astrogliosis following repeated resections may have induced the rare transformation to glioblastoma. Clinical presentation: A patient presenting with left lower extremity weakness was found to harbor a parietal mass lesion. Histopathology demonstrated an epidermoid cyst. Following multiple re-resections, an intra-axial mass was discovered within the operative bed, confirmed as glioblastoma. Conclusion: This is the first report of glioblastoma associated with a resected epidermoid cyst. Subsequent to resection, the chronic inflammatory milieu propagated by astrogliosis is thought to have induced malignancy. The progression to glioblastoma draws attention to neoplastic transformation in the context of recurrent epidermoids

GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor’s shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma’s and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1’s binding with fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 however, TUBB4 expression is unaltered upon fasentin treatment. Using human pluripotent stem cell antibody array, we demonstrate reduced levels of Oct3/4, Nanog, Sox2, Sox17, Snail and VEGFR2 (Vascular endothelial growth factor receptor 2) upon CR-42-24 treatment. Overall, our data confirm that silencing TUBB4 or GLUT1 reduce GSC tumorsphere formation, self-renewal and proliferation in vitro. These findings suggest GLUT1 and its binding partner TUBB4 as druggable targets that warrant further investigation in GBM

GLUT1 and TUBB4 in Glioblastoma Could be Efficacious Targets

Glioblastoma multiforme (GBM) is the most aggressive and deadly brain tumor, portending a median 13-month survival even following gross total resection with adjuvant chemotherapy and radiotherapy. This prognosis necessitates improved therapies for the disease. A target of interest for novel chemotherapies is the Warburg Effect, which describes the tumor’s shift away from oxidative phosphorylation towards glycolysis. Here, we elucidate GLUT1 (Glucose transporter 1) and one of its associated binding partners, TUBB4 (Tubulin 4), as potentially druggable targets in GBM. Using data mining approach, we demonstrate that GLUT1 is overexpressed as a function of tumor grade in astrocytoma’s and that its overexpression is associated with poorer prognosis. Using both mass spectrometry performed on hGBM (human glioblastoma patient specimen) and in silico modeling, we show that GLUT1 interacts with TUBB4, and more accurately demonstrates GLUT1’s binding with fasentin. Proximity ligation assay (PLA) and immunoprecipitation studies confirm GLUT1 interaction with TUBB4. Treatment of GSC33 and GSC28 cells with TUBB4 inhibitor, CR-42-24, reduces the expression of GLUT1 however, TUBB4 expression is unaltered upon fasentin treatment. Using human pluripotent stem cell antibody array, we demonstrate reduced levels of Oct3/4, Nanog, Sox2, Sox17, Snail and VEGFR2 (Vascular endothelial growth factor receptor 2) upon CR-42-24 treatment. Overall, our data confirm that silencing TUBB4 or GLUT1 reduce GSC tumorsphere formation, self-renewal and proliferation in vitro. These findings suggest GLUT1 and its binding partner TUBB4 as druggable targets that warrant further investigation in GBM.</jats:p

Abstract 3535: Methylation regulates HEY1 expression in glioblastoma

Abstract Glioblastoma multiforme (GBM) remains one of the most lethal and difficult-to-treat cancers of the central nervous system despite the existence of multi-modal therapeutic approaches. The poor prognosis in GBM patients is due in part to its resistance to available treatments, which calls for identifying novel molecular therapeutic targets. In this study, we identified an interesting biomarker, Hairy/Enhancer-Of-Split related with YRPW Motif (HEY1), a mediator of Notch signaling, which contributes to the pathogenesis of GBM. Datamining studies and our immunohistochemistry and immunoblot analysis showed that HEY1 is highly expressed in GBM patient specimens. Recent studies indicate that methylation status may control the expression of cancer phenotype. Our studies using bisulphite sequencing on the patient samples showed that HEY1 promoter was hypermethylated in the normal brain when compared to GBM specimens. Treatment on the 4910 and 5310 xenograft cell lines with sodium butyrate (NaB) greatly decreased HEY1 expression owing to its promoter hypermethylation with a concomitant increase in DNMT1 expression confirming that promoter methylation regulate the HEY1 expression in GBM. NaB treatment also induced cell apoptosis as evaluated by flow cytometric analysis. Silencing HEY1 reduced invasion, migration and proliferation in 4910 and 5310 cells. Further, immunoblot and q-PCR analysis demonstrated the existence of a potential positive regulatory loop between HEY1 and p53. Additionally, DNA microarrays with HEY1 recombinant protein demonstrated good correlation with p53 and provided various bonafide targets of HEY1. Collectively, these studies suggest HEY1 as an important predictive marker for GBM, thus indicating a potential target for future GBM therapy. Citation Format: Maheedhara Reddy Guda, Andrew J. Tsung, Swapna Asuthkar, Collin M. Labak, Yining Lu, Sarah E. Martin, Prasad V. Durbaka, Kiran K. Velpula. Methylation regulates HEY1 expression in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3535. doi:10.1158/1538-7445.AM2017-3535</jats:p

Abstract 5433: β-Tubulin inhibitors reduce GLUT1 membrane trafficking to attenuate tumorigenesis in glioblastoma subtypes

Abstract Glioblastoma is an aggressive, high-grade tumor with poor prognosis due to lack of sound therapeutic options. Mesenchymal subtype GBMs are particularly difficult to treat because they tend to proliferate in the sub ventricular zone, an area that breeds stem-like neural cells and proves nearly impossible to access for surgical resection. They also contribute to creating a hypoxic microenvironment and switch to glycolytic metabolism in what is known as the Warburg Effect. Here, we hypothesize that strategically inhibiting the glucose transporter, GLUT1, through cytoskeletal components that traffic it to the cell membrane may reverse the Warburg Effect, attenuating further tumorigenesis and decreasing the stemness of such cells. Datamining studies and immunoblot analysis conducted on human glioblastoma patient specimens (hGBM) demonstrated that GLUT1 is highly upregulated. Limiting dilution assay conducted using GLUT1 inhibitors- fasentin and 2-Deoxy-D-glucose reduced the proliferation in mesenchymal cancer stem cell (CSC) subtype in in vitro culture. Simultaneously, mass spectrometric analysis revealed significant association between GLUT1 and β-tubulin 4 (TUBB4) in mesenchymal subtyped cells. This association was further confirmed by large-sample datamining and in immunoprecipitation studies from hGBM specimens, suggesting that TUBB4 may be a viable target in deterring the trafficking of upregulated GLUT1 to the membrane. Collectively, these studies confirm that GLUT1 is associated with TUBB4, and that targeting TUBB4 via siRNA or colchicine derivatives could prove effective in reversing the Warburg Effect in GBM cells and ultimately improve patient outcomes. Citation Format: Collin M. Labak, Maheedhara R. Guda, Swapna Asuthkar, Neha Jain, Yining Lu, Ian Purvis, Jack Tuszynski, Ichiro Nakano, Andrew J. Tsung, Kiran K. Velpula. β-Tubulin inhibitors reduce GLUT1 membrane trafficking to attenuate tumorigenesis in glioblastoma subtypes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5433. doi:10.1158/1538-7445.AM2017-5433</jats:p