Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-009-9919-z) contains supplementary material, which is available to authorized users.

Background and Aims A variety of auto‐antibody assays are available as part of the clinical care of patients with liver disease. We sought to better understand the clinical utility of immune serological testing in patients with primary biliary cholangitis (PBC). Methods We retrospectively analysed data from 2846 patients investigated for liver disease at a UK liver centre between 2001 and 2017. A total of 499 patients with PBC were identified. Immune serology results were examined for their diagnostic utility and prognostic significance to predict transplant‐free survival. Results Antimitochondrial antibodies (AMAs) were specific (94.5%) and sensitive (85.6%) for PBC; antinuclear antibodies (ANAs) against glycoprotein 210 (gp210) and sp100 were specific (>98%) but not sensitive (<25%). The disease‐specific ANAs were detectable in 29.6% of AMA‐negative patients. Anti‐gp210 auto‐antibodies were significantly associated with elevated serum aminotransferase activity, bilirubin and liver stiffness at presentation (P < .010). Anti‐gp210 auto‐antibodies predicted non‐response to ursodeoxycholic acid (UDCA) by GLOBE criteria (39.3% vs 16.7%, P = .005). Moreover, anti‐gp210 was independently associated with death or liver transplantation (HR 3.22, 95% CI 1.49‐6.96; P = .003), after accounting for other significant baseline determinants of outcome. Serologic finding of anti‐gp210 antibodies conferred an independent risk of death or transplantation (HR 4.13, 95% CI 1.85‐9.22; P = .001) after accounting for treatment response. Conclusion In our single‐centre cohort of patients with PBC, the presence of anti‐gp210 was associated with an adverse presenting phenotype, predicted treatment non‐response and independently predicted reduced transplant‐free survival.

No abstract

No abstract

Angle-resolved particle image velocimetry measurements were conducted at one degree intervals in miniature vessels of four different configurations used in high-throughput experimentation. The four vesselsstandard fully baffled, unbaffled, off-center or eccentric impeller, and square sectionwere agitated by an up-pumping six-blade 45° pitched blade turbine (PBT). The effect of periodicity was revealed in all configurations but was restricted to the impeller discharge and inflow regions. The square vessel achieved the strongest axial-radial flow field among all configurations. The smallest overestimation in the computation of turbulent kinetic energy by the ensemble time average method, otherwise referred to as pseudoturbulence, was achieved in the eccentric and square configurations. The up-pumping PBT shed trailing vortices mainly in a radial direction with relatively little axial movement. The highest axial vortex position was achieved in the square vessel, which may be partly responsible for its lower mixing time compared to other configurations. The measurements obtained here in the high-transitional regime suggest that the square configuration performs better than other configurations and can be a good replacement for the fully baffled vessel in commercial high-throughput experimentation units where baffles are usually prohibited. This result was confirmed from mixing time measurements made using planar laser induced fluorescence where the superiority of the square vessel was demonstrated.