15 hasil untuk "Max Nobis"
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Artikel Jurnal
A non-genetic, cell cycle-dependent mechanism of platinum resistance in lung adenocarcinoma
We previously used a pulse-based in vitro assay to unveil targetable signalling pathways associated with innate cisplatin resistance in lung adenocarcinoma (Hastings et al., 2020). Here, we advanced this model system and identified a non-genetic mechanism of resistance that drives recovery and…
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Artikel Jurnal
Monocyte-hitchhiking system for the targeted delivery of paclitaxel-loaded PLGA nanoparticles to glioblastoma in mice
Abstract Cell-based therapy for the treatment of glioblastoma (GBM) has gained a lot of attention as a minimally invasive drug delivery strategy because of its potential to overcome the blood–brain barrier (BBB) impediment and target the tumor microenvironment. Here, we evaluate the targeting…
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An autophagy program that promotes T cell egress from the lymph node controls responses to immune checkpoint blockade
Summary: Lymphatic endothelial cells (LECs) of the lymph node (LN) parenchyma orchestrate leukocyte trafficking and peripheral T cell dynamics. T cell responses to immunotherapy largely rely on peripheral T cell recruitment in tumors. Yet, a systematic and molecular understanding of how LECs within…
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Removing physiological motion from intravital and clinical functional imaging data
Intravital microscopy can provide unique insights into the function of biological processes in a native context. However, physiological motion caused by peristalsis, respiration and the heartbeat can present a significant challenge, particularly for functional readouts such as fluorescence lifetime…
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Artikel Jurnal
The Rac-FRET Mouse Reveals Tight Spatiotemporal Control of Rac Activity in Primary Cells and Tissues
The small G protein family Rac has numerous regulators that integrate extracellular signals into tight spatiotemporal maps of its activity to promote specific cell morphologies and responses. Here, we have generated a mouse strain, Rac-FRET, which ubiquitously expresses the Raichu-Rac biosensor. It…
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Artikel Jurnal
Peripheral-specific Y1 receptor antagonism increases thermogenesis and protects against diet-induced obesity
Neuropeptide Y signalling in the periphery contributes to the regulation of metabolic and energy homeostasis. Here the authors show that blocking Y1R signalling in peripheral tissues using the selective antagonist BIBO3304 ameliorates diet-induced obesity and improves whole-body glucose metabolism.
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Artikel Jurnal
Targeting promiscuous heterodimerization overcomes innate resistance to ERBB2 dimerization inhibitors in breast cancer
Abstract Background The oncogenic receptor tyrosine kinase (RTK) ERBB2 is known to dimerize with other EGFR family members, particularly ERBB3, through which it potently activates PI3K signalling. Antibody-mediated inhibition of this ERBB2/ERBB3/PI3K axis has been a cornerstone of treatment for…
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Artikel Jurnal
Intravital Imaging to Monitor Therapeutic Response in Moving Hypoxic Regions Resistant to PI3K Pathway Targeting in Pancreatic Cancer
Summary: Application of advanced intravital imaging facilitates dynamic monitoring of pathway activity upon therapeutic inhibition. Here, we assess resistance to therapeutic inhibition of the PI3K pathway within the hypoxic microenvironment of pancreatic ductal adenocarcinoma (PDAC) and identify a…
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Artikel Jurnal
Temporal profiling of the breast tumour microenvironment reveals collagen XII as a driver of metastasis
The distribution and organisation of matrix molecules in the tumour stroma help shape solid tumour progression. Here they perform temporal proteomic profiling of the matrisome during breast cancer progression and show that collagen XII secreted from CAFs provides a pro-invasive microenvironment.
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Artikel Jurnal
Intravital FRAP Imaging using an E-cadherin-GFP Mouse Reveals Disease- and Drug-Dependent Dynamic Regulation of Cell-Cell Junctions in Live Tissue
E-cadherin-mediated cell-cell junctions play a prominent role in maintaining the epithelial architecture. The disruption or deregulation of these adhesions in cancer can lead to the collapse of tumor epithelia that precedes invasion and subsequent metastasis. Here we generated an E-cadherin-GFP…
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Artikel Jurnal
CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan
Subtypes of cancer associated fibroblasts can both promote and suppress tumorigenesis. Here, the authors investigate how p53 status in pancreatic cancer cells affects their interaction with cancer associated fibroblasts, and report perlecan as a mediator of the pro-metastatic environment.
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Artikel Jurnal
Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling
Abstract The estrogen receptor (ER) drives growth in most breast cancers. Endocrine therapy reduces recurrence, however around 30% of cancers relapse. Many recurrences occur years later, with slowly proliferating, hard-to-treat disease. To study this, we generate slow-growing resistant cells that…
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Optimizing metastatic-cascade-dependent Rac1 targeting in breast cancer: Guidance using optical window intravital FRET imaging
Summary: Assessing drug response within live native tissue provides increased fidelity with regards to optimizing efficacy while minimizing off-target effects. Here, using longitudinal intravital imaging of a Rac1-Förster resonance energy transfer (FRET) biosensor mouse coupled with in vivo…
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Artikel Jurnal
A RhoA-FRET Biosensor Mouse for Intravital Imaging in Normal Tissue Homeostasis and Disease Contexts
The small GTPase RhoA is involved in a variety of fundamental processes in normal tissue. Spatiotemporal control of RhoA is thought to govern mechanosensing, growth, and motility of cells, while its deregulation is associated with disease development. Here, we describe the generation of a…
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Artikel Jurnal
Tumor Biomechanics Alters Metastatic Dissemination of Triple Negative Breast Cancer via Rewiring Fatty Acid Metabolism
Abstract In recent decades, the role of tumor biomechanics on cancer cell behavior at the primary site has been increasingly appreciated. However, the effect of primary tumor biomechanics on the latter stages of the metastatic cascade, such as metastatic seeding of secondary sites and outgrowth…