scholarly journals In vivo optical spectroscopy for improved detection of pancreatic adenocarcinoma: a feasibility study

2013 ◽  
Vol 5 (1) ◽  
pp. 9 ◽  
Author(s):  
William R. Lloyd ◽  
Robert H. Wilson ◽  
Seung Yup Lee ◽  
Malavika Chandra ◽  
Barbara McKenna ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Optical Spectroscopy ◽  
Feasibility Study

Visualization of brain microvasculature and blood flow in vivo: Feasibility study using confocal laser endomicroscopy

2021 ◽  
Author(s):  
Evgenii Belykh ◽  
Xiaochun Zhao ◽  
Brandon Ngo ◽  
Dara S. Farhadi ◽  
Adam Kindelin ◽  
...  
Keyword(s):  
Blood Flow ◽  
Feasibility Study ◽  
Confocal Laser Endomicroscopy ◽  
Confocal Laser ◽  
Brain Microvasculature

scholarly journals High potency STING agonists engage unique myeloid pathways to reverse pancreatic cancer immune privilege

2021 ◽  
Vol 9 (8) ◽  
pp. e003246
Author(s):  
Casey R Ager ◽  
Akash Boda ◽  
Kimal Rajapakshe ◽  
Spencer Thomas Lea ◽  
Maria Emilia Di Francesco ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Pancreatic Adenocarcinoma ◽  
T Cell Activation ◽  
Cell Activation ◽  
Suppressor Cells ◽  
Intratumoral Injection ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
High Potency

BackgroundIntratumoral injection of cyclic dinucleotide (CDN) agonists of the stimulator of interferon genes (STING) pathway engages innate immune activation and priming of adaptive immune effectors to foster local and distal tumor clearance. Despite proven therapeutic efficacy in preclinical models, a thorough understanding of how CDNs reprogram suppressive myeloid stroma in mouse and man is lacking.MethodsHere, we perform deep transcript-level and protein-level profiling of myeloid-derived suppressor cells and M2 macrophages following stimulation with CDNs of ascending potency. Additionally, we leverage orthotopic Kras+/G12DTP53+/R172HPdx1-Cre (KPC) derived models of pancreatic adenocarcinoma (PDAC) to determine the capacity for locally administered CDNs to sensitize PDAC to immune checkpoint blockade. We use bioluminescent in vivo imaging and 30-parameter flow cytometry to profile growth kinetics and remodeling of the tumor stroma post-therapy.ResultsHighly potent synthetic STING agonists repolarize suppressive myeloid populations of human and murine origin in part through inhibition of Myc signaling, metabolic modulation, and antagonism of cell cycle. Surprisingly, high-potency synthetic agonists engage qualitatively unique pathways as compared with natural CDNs. Consistent with our mechanistic observations, we find that intratumoral injection of the highest activity STING agonist, IACS-8803, into orthotopic pancreatic adenocarcinoma lesions unmasks sensitivity to checkpoint blockade immunotherapy. Dimensionality reduction analyses of high parameter flow cytometry data reveals substantial contributions of both myeloid repolarization and T cell activation underlying the in vivo therapeutic benefit of this approach.ConclusionsThis study defines the molecular basis of STING-mediated myeloid reprogramming, revealing previously unappreciated and qualitatively unique pathways engaged by CDNs of ascending potency during functional repolarization. Furthermore, we demonstrate the potential for high potency CDNs to overcome immunotherapy resistance in an orthotopic, multifocal model of PDAC.

Human pancreatic adenocarcinoma: In vitro and in vivo morphology of a new tumor line established from ascites

In Vitro ◽  
1982 ◽  
Vol 18 (1) ◽  
pp. 24-34 ◽  
Author(s):  
W. H. Chen ◽  
J. S. Horoszewicz ◽  
S. S. Leong ◽  
T. Shimano ◽  
R. Penetrante ◽  
...  
Keyword(s):  
Pancreatic Adenocarcinoma ◽  
Tumor Line ◽  
Human Pancreatic Adenocarcinoma

Interphalangeal Joint Cartilage: High-Spatial-Resolution in Vivo MR T2 Mapping—A Feasibility Study

Radiology ◽  
2004 ◽  
Vol 233 (1) ◽  
pp. 292-296 ◽  
Author(s):  
Jelena Lazovic-Stojkovic ◽  
Timothy J. Mosher ◽  
Harvey E. Smith ◽  
Qing X. Yang ◽  
Bernard J. Dardzinski ◽  
...  
Keyword(s):  
Feasibility Study ◽  
Spatial Resolution ◽  
High Spatial Resolution ◽  
T2 Mapping ◽  
Interphalangeal Joint ◽  
Joint Cartilage
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