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Biology subjects

Kingsmore, K. M.

Publications and source records attributed to Kingsmore, K. M..

3 recordsLinked to original sources

Interstitial fluid transport dynamics predict glioblastoma invasion and progression

Glioblastoma is characterized by aggressive infiltration into surrounding brain tissue, hindering complete surgical resection and contributing to poor patient outcomes. Identifying tumor-specific invasion patterns is essential for advancing our understanding of glioblastoma progression and improving surgical and radiotherapeutic strategies. Here, we leverage in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to noninvasively quantify interstitial fluid velocity, direction, and diffusion within and around glioblastomas. We introduce a novel vector-based pathline analysis to trace downstream accumulation of fluid flow originating from the tumor core, providing a spatially explicit perspective on local flow patterns. We find that localized fluid transport metrics predict glioblastoma invasion and progression, offering a new framework to non-invasively identify high-risk regions and guide targeted treatment approaches. One sentence summaryInvasion and progression of glioblastoma can be predicted with interstitial fluid flow patterns via magnetic resonance imaging.

bioengineering↗

Comprehensive Transcriptomic Analysis of COVID-19 Blood, Lung, and Airway

AbstractSARS-CoV2 is a previously uncharacterized coronavirus and causative agent of the COVID-19 pandemic. The host response to SARS-CoV2 has not yet been fully delineated, hampering a precise approach to therapy. To address this, we carried out a comprehensive analysis of gene expression data from the blood, lung, and airway of COVID-19 patients. Our results indicate that COVID-19 pathogenesis is driven by populations of myeloid-lineage cells with highly inflammatory but distinct transcriptional signatures in each compartment. The relative absence of cytotoxic cells in the lung suggests a model in which delayed clearance of the virus may permit exaggerated myeloid cell activation that contributes to disease pathogenesis by the production of inflammatory mediators. The gene expression profiles also identify potential therapeutic targets that could be modified with available drugs. The data suggest that transcriptomic profiling can provide an understanding of the pathogenesis of COVID-19 in individual patients. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=168 HEIGHT=200 SRC="FIGDIR/small/121889v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@7dccedorg.highwire.dtl.DTLVardef@1190e1forg.highwire.dtl.DTLVardef@1ee2e67org.highwire.dtl.DTLVardef@289f72_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

Convective forces increase CXCR4-dependent glioblastoma cell invasion in GL261 murine model

Glioblastoma is the most common and malignant form of brain cancer. Its invasive nature limits treatment efficacy and promotes inevitable recurrence. Previous in vitro studies have shown that interstitial fluid flow, a factor characteristically increased in cancer, increases glioma cell invasion via CXCR4-CXCL12. It is currently unknown if these effects translate in vivo. Using the therapeutic technique of convection enhanced delivery (CED), we tested if convective flow alters glioma invasion in vivo using the syngeneic GL261 mouse model of glioblastoma. We first confirmed that GL261 invasion in vitro increased under flow in a CXCR4-CXCL12 dependent manner. Additionally, approximately 65.4% and 6.59% of GL261 express CXCR4 and CXCL12 in vivo, respectively, with 3.38% expressing both. Inducing convective flow within implanted tumors indeed increased glioma cell invasion over untreated controls, and administering CXCR4 antagonist AMD3100 (5 mg/kg) effectively eliminated this response. Therefore, glioma invasion is in fact stimulated by convective flow in vivo through CXCR4. We also analyzed patient samples to show that expression of CXCR4 and CXCL12 increase in patients following therapy. These results suggesting that targeting flow-stimulated invasion may prove beneficial as a second line of therapy, particularly in patients chosen to receive convection enhanced drug delivery.

cancer biology↗