Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12–15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication.
The effects of the variations in concentrations of hydrogen (0−480 mol/m3) and 1-butene (0−380 mol/m3) on the gas-phase copolymerization of ethylene and 1-butene over a MgCl2/SiO2-supported Ti catalyst were investigated using a semibatch reactor operated at 70 °C. Polymers were characterized by size exclusion chromatography (SEC), melt flow index, analytical and preparative temperature-rising elution fractionation (ATREF and PTREF), and PTREF−SEC cross-fractionation. Excellent correlations were obtained between the reactor operating conditions and polymer properties; e.g., the average polymerization rate was proportional to 1/(1 + a[H2]0.5), the methyl group concentration in the polymer was proportional to the 1-butene concentration, and the melt flow index varied as Mw-3.4. The most significant finding was that the hydrogen concentration dependence of the termination rate by hydrogen was different for different catalytic sites; the termination rate was first order for the catalytic sites responsible for the formation of copolymer and half-order for the sites responsible for the homopolymer component of the polymer.
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