Targeting EGFR Induced Oxidative Stress by PARP1 Inhibition in Glioblastoma Therapy

Despite the critical role of Epidermal Growth Factor Receptor (EGFR) in glioblastoma pathogenesis [1,2], EGFR targeted therapies have achieved limited clinical efficacy [3]. Here we propose an alternate therapeutic strategy based on the conceptual framework of non-oncogene addiction [4,5]. A directed RNAi screen revealed that glioblastoma cells overexpressing EGFRvIII [6], an oncogenic variant of EGFR, become hyper-dependent on a variety of DNA repair genes. Among these, there was an enrichment of Base Excision Repair (BER) genes required for the repair of Reactive Oxygen Species (ROS)-induced DNA damage, including poly-ADP ribose polymerase 1 (PARP1). Subsequent studies revealed that EGFRvIII overexpression in glioblastoma cells caused increased levels of ROS, DNA strand break accumulation, and genome instability. In a panel of primary glioblastoma lines, sensitivity to PARP1 inhibition correlated with the levels of EGFR activation and oxidative stress. Gene expression analysis indicated that reduced expression of BER genes in glioblastomas with high EGFR expression correlated with improved patient survival. These observations suggest that oxidative stress secondary to EGFR hyperactivation necessitates increased cellular reliance on PARP1 mediated BER, and offer critical insights into clinical trial design.

Autologous scleral patch graft in tube shunt surgery

Purpose . To investigate alternative surgical method to cover subconjunctival portion of the tube in tube shunt surgery in glaucoma Methods. In thirteen eyes of twelve patients who underwent tube shunt surgery at WEH between July 1991 to November 1996 a "rotating" autologous scleral lamellar graft was created to cover the subconjuctival course of the tube. These patients were followed for clinical signs of conjuctival breakdown, graft melt, tube erosion, anterior staphylomas, graft related inflammation, infections or graft related complications. Results. The patients were followed up for a mean of 16 5 months( range 1-60 months). All eyes tolerated the autologous graft well without any clinical evidence of tube erosions, graft melting , graft related or intraocular inflammation Conclusions The use of autologous sciera, to cover the tube in a tube shunt procedure appears to be effective and without inappropriate short term risk. It offers the advantages of availability , lower cost, and eliminates the potential risk of transmission of infectious disease( i.e. slow-virus, HIV etc.).

An integrated wideband multifunctional antenna using a microstrip patch with two U-slots

In this paper a multifunctional microstrip antenna is designed, fabricated and experimentally verified for operation in AWS, GSM, WiMAX and WLAN bands. This microstrip patch antenna has two U-shaped slots to achieve the dual wideband operation required to meet these specifications. The dimensions and locations of the U-slots are designed appropriately. The thick substrate used here helps in integrating the antenna with the existing aircraft panel material while achieving wide bandwidths. Experimental results of this single feed antenna indicate that it meets all current requirements for in-cabin wireless communication needs.

A double U-slot patch antenna with dual wideband characteristics

Microstrip patch antennas are strong candidates for use in many wireless communications applications. This paper proposes the use of a patch antenna with two U-shaped slots to achieve dual band operation. A thick substrate helps broaden the individual bandwidths. The antenna is designed based on extensive IE3D simulation studies. A prototype antenna is fabricated and experimentally verified for the required performance.