Biology subjects

Foster, B.

Publications and source records attributed to Foster, B..

3 recordsLinked to original sources

bioRxiv2018

CTC Marker CD117/c-kit Represents a Prostate Cancer Stem-Like Subpopulation Driving Progression, Migration, and TKI Resistance

Cancer stem-like cells (CSCs) are associated with cancer progression, metastasis, and recurrence, and may also represent a subset of circulating tumor cells (CTCs). In our prior study, CTCs in advanced prostate cancer patients were found to express CD117/c-kit in a liquid biopsy. Whether CD117 expression played an active or passive role in the aggressiveness and migration of these CTCs remained an open question. In this study, we show that CD117 expression in prostate cancer patients is associated with decreased overall and progression-free survival and that activation and phosphorylation of CD117 increases in prostate cancer patients with higher Gleason grades. To determine how CD117 expression and activation by its ligand stem cell factor (SCF, kit ligand, steel factor) alter prostate cancer aggressiveness, we used LNCaP-C4-2 and PC3-mm human prostate cancer cells, which contain a CD117+ subpopulation. We demonstrate that CD117+ cells display increased proliferation and migration. In prostaspheres, CD117 expression enhances sphere formation. In both 2D and 3D cultures, stemness marker gene expression is higher in CD117+ cells. Using xenograft limiting dilution assays and serial tumor initiation assays, we show that CD117+ cells represent a CSC population. Combined, these data indicate that CD117 expression potentially promotes tumor initiation and metastasis. Further, in cell lines, CD117 activation by SCF promotes faster proliferation and invasiveness, while blocking CD117 activation with tyrosine kinase inhibitors (TKIs) decreased progression in a context-dependent manner. We demonstrate that CD117 expression and activation drives prostate cancer aggressiveness through the CSC phenotype and TKI resistance.

cancer biology↗

bioRxiv2018

Rules Governing Perception of Multiple Phosphenes by Human Observers

Stimulation of single sites in primary visual cortex results in the perception of a small flash of light known as a phosphene. Little is known about how phosphenes from multiple electrodes can be combined to form perception of coherent patterns. Here we examine the percepts reported by human observers as various spatial configurations of 2 to 5 electrodes in visual cortex were stimulated simultaneously. When two electrodes were stimulated simultaneously, subjects reliably perceived either one or two phosphenes depending on the physical distance separating the electrodes. In cases where two phosphenes were perceived, they were located in the same visual field location as when the two electrodes were stimulated separately. Adding a third electrode produced similar results. In several subjects, we obtained combination of 4 to 5 electrodes that generated individual phosphenes when stimulated concurrently. Subjects were able to reliably discriminate between different multiple electrode stimulation patterns that were presented in random order. These results demonstrate that simple pattern information can be conveyed to subjects with surface electrodes spaced at millimeters apart on the cortex.

neuroscience↗

bioRxiv2018

Sex-dependent Relationship Between Wrist Deviation and Scaphoid Kinematics

Several methods of describing patterns of carpal kinematics from radiographs have emerged due to their potential use in developing personalized treatments for wrist pathologies. Such radiography-derived metrics have been used to infer associations between patterns of scaphoid kinematics and other clinically relevant factors such as sex, but the simultaneous effects of sex and wrist position on scaphoid kinematic metrics has yet to be considered. We sought to investigate the relationship between wrist position in the coronal plane and radiographic measurements of the scaphoid for each sex independently, then identify sex-specific differences in scaphoid measurements and calculated metrics. We retrospectively identified 38 subjects with posteroanterior radial and ulnar deviation radiographs. Radiographic scaphoid measurements were collected and used to calculate five scaphoid kinematic metrics per participant. We used Pearson correlation coefficients to explore the relationships between the degrees of wrist deviation in the coronal plane and radiographic scaphoid measurements for men and women independently. We used the non-parametric Wilcoxon signed-rank test to compare values between sexes. The correlations between degrees of coronal wrist deviation and radiographic measurements of scaphoid inclination were significant only for men. Men also had significantly greater values for all radiographic scaphoid measurements. Our study demonstrated sex-specific differences in the relationship between the degrees of radial and ulnar wrist deviation and scaphoid positioning.\n\nClinical RelevanceOur findings show the importance of stratifying by sex in studies of carpal kinematics, such as scaphoid kinematics, and that investigation of strategies to restore normal carpal function should incorporate sex as a biological variable.

physiology↗