NOTCH blockade combined with radiation therapy and temozolomide prolongs survival of orthotopic glioblastoma.

Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation resistance and intrinsic or acquired TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The NOTCH signaling pathway is expressed and active in human glioblastoma and NOTCH inhibitors attenuate tumor growth in vivo in xenograft models. Here we show using an image guided micro-CT and precision radiotherapy platform that a combination of the clinically approved NOTCH/γ-secretase inhibitor (GSI) RO4929097 with standard of care (TMZ + RT) reduces tumor growth and prolongs survival compared to dual combinations. We show that GSI in combination with RT and TMZ attenuates proliferation, decreases 3D spheroid growth and results into a marked reduction in clonogenic survival in primary and established glioma cell lines. We found that the glioma stem cell marker CD133, SOX2 and Nestin were reduced following combination treatments and NOTCH inhibitors albeit in a different manner. These findings indicate that NOTCH inhibition combined with standard of care treatment has an anti-glioma stem cell effect which provides an improved survival benefit for GBM and encourages further translational and clinical studies

Monitoring of effluent water quality of SEKA Dalaman Pulp and Paper Industry

This paper presents results of monitoring data of the full scale wastewater treatment system treating leached kraft pulp and paper industry effluents. The treatment system has a full-scale aerated lagoon system treating effluents from a chemical pretreatment plant. The colored effluents from the treatment plant has been discharges to a river ending at Mediterranean, Marine outfall system is under construction to prevent color problem, Statistical Analysis is performed on 29 months monitoring data

Biological treatability of raw and ozonated synthetic penicillin formulation effluent

Chemical pre-treatment of synthetic Procaine Penicillin G (PPG) effluent with ozone (applied dose =1440mg/h; treatment duration =60min) at pH =7 was investigated. Successive biological treatability studies were performed with raw, ozonated penicillin formulation effluent and synthetic readily biodegradable substrate as simulated domestic wastewater. The PPG effluent additions were adjusted to constitute approximately 30% of the total COD in the reactor. Ozonation of PPG effluent resulted in practically complete removal of the parent pollutant accompanied by 40% COD abatement. Speaking for the raw PPG effluent, prolonged acclimation periods were necessary to obtain significant COD removal efficiencies. Batch activated sludge treatment experiments and respirometric studies have demonstrated that the selection of true retention time is extremely crucial for having high amount of slowly hydrolysable substrate or complex wastewater, like pharmaceutical effluent. The effect of ozonation time on biological treatability performance of PPG has been evaluated in the study. Pre-ozonation of PPG effluent did not improve its ultimate biodegradability.</jats:p