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1.
ACS Sens ; 7(11): 3379-3388, 2022 11 25.
Article in English | MEDLINE | ID: mdl-36374944

ABSTRACT

Improving outcomes for cancer patients during treatment and monitoring for cancer recurrence requires personalized care which can only be achieved through regular surveillance for biomarkers. Unfortunately, routine detection for blood-based biomarkers is cost-prohibitive using currently specialized laboratories. Using a rapid self-assembly sensing interface amenable to methods of mass production, we demonstrate the ability to detect and quantify a small carbohydrate-based cancer biomarker, Tn antigen (αGalNAc-Ser/Thr) in a small volume of blood, using a test format strip reminiscent of a blood glucose test. The detection of Tn antigen at picomolar levels is achieved through a new transduction mechanism based on the impact of Tn antigen interactions on the molecular dynamic motion of a lectin cross-linked lubricin antifouling brush. In tests performed on retrospective blood plasma samples from patients presenting three different tumor types, differentiation between healthy and diseased patients was achieved, highlighting the clinical potential for cancer monitoring.


Subject(s)
Neoplasms , Point-of-Care Systems , Humans , Retrospective Studies , Neoplasms/diagnosis , Carbohydrates
2.
J Autoimmun ; 88: 131-138, 2018 03.
Article in English | MEDLINE | ID: mdl-29103803

ABSTRACT

OBJECTIVE: Antiphospholipid syndrome (APS) is a systemic autoimmune disorder of young adults associated with devastating pregnancy complications (recurrent miscarriages, preeclampsia and low birth weight) and vascular complications including thrombosis. The key components implicated in pathogenesis of APS are the complement cascade and tissue factor (TF) activity causing inflammation and coagulation. Purinergic signalling involving catabolism of ATP to adenosine by cell-surface enzymes CD39 and CD73 has anti-inflammatory and anti-thrombotic effects. We studied whether activities of CD39 and CD73 are important in preventing the development of miscarriages in APS. METHODS: We studied frequency of miscarriages and decidual pathology following passive transfer of human aPL-ab to pregnant wildtype mice, and mice deficient in CD39 and CD73, and also transgenic mice exhibiting 2-3X higher CD39 activity. RESULTS: aPL-ab infusion in pregnant CD39-or CD73-knockout mice triggers an increase in miscarriages, associated with increased TF expression and complement deposition as well as elevated oxidative stress and pro-inflammatory TNF-α and IL-10 expression within the placental decidua. In contrast, aPL-ab induced miscarriages are prevented in mice over-expressing CD39, with reduced decidual TF expression and C3d deposition, diminished lipid peroxidation (4-hydroxynonenal or 4-HNE positive lipid adducts), and reduced TNF-α expression. CONCLUSION: We demonstrate a protective role for CD39 in APS and provide rationale for both the development of endothelial cell-targeted soluble CD39 as a novel therapeutic for APS and analysis of perturbations in the purinergic pathway to explain human disease.


Subject(s)
Abortion, Spontaneous/immunology , Antibodies, Antiphospholipid/metabolism , Antigens, CD/metabolism , Antiphospholipid Syndrome/immunology , Apyrase/metabolism , Pregnancy Complications/immunology , 5'-Nucleotidase/genetics , 5'-Nucleotidase/metabolism , Adult , Animals , Antigens, CD/genetics , Apyrase/genetics , Complement C3d/metabolism , Disease Models, Animal , Female , Humans , Immunization, Passive , Inflammation , Inflammation Mediators/metabolism , Lipid Peroxidation , Mice , Mice, Knockout , Mice, Transgenic , Pregnancy , Thromboplastin/metabolism , Tumor Necrosis Factor-alpha/metabolism
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