ABSTRACT
The molecular mechanisms that regulate breast cancer cell (BCC) metastasis and proliferation within the leptomeninges (LM) are poorly understood, which limits the development of effective therapies. In this work, we show that BCCs in mice can invade the LM by abluminal migration along blood vessels that connect vertebral or calvarial bone marrow and meninges, bypassing the blood-brain barrier. This process is dependent on BCC engagement with vascular basement membrane laminin through expression of the neuronal pathfinding molecule integrin α6. Once in the LM, BCCs colocalize with perivascular meningeal macrophages and induce their expression of the prosurvival neurotrophin glial-derived neurotrophic factor (GDNF). Intrathecal GDNF blockade, macrophage-specific GDNF ablation, or deletion of the GDNF receptor neural cell adhesion molecule (NCAM) from BCCs inhibits breast cancer growth within the LM. These data suggest integrin α6 and the GDNF signaling axis as new therapeutic targets against breast cancer LM metastasis.
Subject(s)
Bone Neoplasms , Breast Neoplasms , Integrin alpha6 , Meningeal Neoplasms , Meninges , Neural Pathways , Animals , Female , Humans , Mice , Basement Membrane/metabolism , Bone Neoplasms/secondary , Bone Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Cell Line, Tumor , Cell Movement , Glial Cell Line-Derived Neurotrophic Factor/genetics , Glial Cell Line-Derived Neurotrophic Factor/metabolism , Integrin alpha6/metabolism , Laminin/metabolism , Macrophages/metabolism , Meningeal Neoplasms/metabolism , Meningeal Neoplasms/secondary , Meninges/pathology , Neoplasm Invasiveness , Neural Cell Adhesion Molecules/metabolism , Neural Cell Adhesion Molecules/genetics , Signal Transduction , Neural Pathways/metabolism , Mice, SCID , Mice, KnockoutABSTRACT
The electrochemical CO2 reduction reaction (CO2RR) in gas-fed flow electrolyzers using gas diffusion electrodes (GDEs) generates industrially relevant activities and provides a promising approach for carbon recycling. Developing effective catalyst systems on GDEs is critical for achieving high activities. Catalyst-polymer composites (CPCs) formed between immobilized molecular catalysts and coordinating polymers exhibit positive synergies for the enhancement of CO2RR activity. However, previous studies of CPCs have been primarily confined to liquid reaction platforms, and there are few examples of translating CPCs to GDE architectures. This suggests a knowledge gap exists in translating between the two platforms. Herein, we identify and bridge that gap by demonstrating a case study for the (poly-4-vinylpyridine)-encapsulated cobalt phthalocyanine (CoPc-P4VP) CPC. We identify a major knolwedge gap in the overlooked factor of CPC's hydrophobicity, which plays a significant role in gas-fed CO2RR but is often neglected in fundamental studies conducted on the liquid reaction platform. We bridge this gap by correlating catalyst hydrophobicity in liquid CO2RR with activity in gas-fed CO2RR by means of water contact angle measurements. Our case study underscores the importance of incorporating an engineering perspective into CPC studies and the necessity to consider hydrophobicity in CPC design and evaluation. This approach will hopefully accelerate the applied studies of this group of promising catalytic materials in gas-fed CO2 electrolysis.
ABSTRACT
Spinal cord stimulation is a successful and thoroughly documented procedure in treating chronic refractory pain. Complications are rare and usually mild, but hardware complications such as electrode dysfunction have been shown to be detrimental in treatment efficacy and patient outcome. We report a case in which a patient diagnosed with complex regional pain syndrome underwent spinal cord stimulation for pain management and experienced lead migration and fracture, resulting in loss of paresthesia and increased pain. This case provides useful clinical information on identifying electrode dysfunction in patients with implanted spinal cord stimulators and emphasizes the importance of preventative measures to reduce the risk of similar complications.
