Publications by authors named "Marianne S M Issac"

Coronavirus disease 2019 (COVID-19) in kidney transplant recipients is a subject of much debate and became of interest to nephrologists amidst the pandemic. The main concerns are the influence of the chronic use of immunosuppressive drugs, the viral-related risk of acute rejection, and the long-term outcome of allograft function. This single-center prospective study included kidney transplant recipients with COVID-19 infection.

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Article Synopsis
  • - Obesity can cause inflammation in the body and make cancer spread faster, especially breast cancer spreading to the lungs.
  • - Researchers discovered that certain immune cells called monocytes work with other immune cells called neutrophils to help breast cancer spread in people who are obese.
  • - They found that these monocytes change and become more active when someone is obese, which helps in the cancer spreading process.
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Background: It has recently been reported that mismatch repair (MMR) status and microsatellite instability (MSI) status in gastroesophageal carcinomas predict surgical, chemotherapeutic and immunotherapeutic outcomes; however, there is extensive variability in the reported incidence and clinical implications of MMR/MSI status in gastroesophaegal adenocarcinomas. We characterized a Canadian surgical patient cohort with respect to MMR status, clinicopathologic correlates and anatomic tumour location.

Methods: We investigated MMR and BRAF V600E status of gastroesophaegal adenocarcinomas in patients who underwent gastrectomy or esophagectomy with extended (D2) lymphadenectomy at a single centre between 2011 and 2019.

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Metastasis is the leading cause of cancer-related deaths, and obesity is associated with increased breast cancer (BC) metastasis. Preclinical studies have shown that obese adipose tissue induces lung neutrophilia associated with enhanced BC metastasis to this site. Here we show that obesity leads to neutrophil-dependent impairment of vascular integrity through loss of endothelial adhesions, enabling cancer cell extravasation into the lung.

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Microabstract: Integration of Next Generation Sequencing (NGS) information for use in distinguishing between Multiple Primary Lung Cancer and intrapulmonary metastasis was evaluated. We used a probabilistic model, comprehensive histologic assessment and NGS to classify patients. Integrating NGS data confirmed initial diagnosis (n = 41), revised the diagnosis (n = 12), while resulted in non-informative data (n = 8).

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The impact of epithelial-mesenchymal transition (EMT) signature on the immune infiltrate present in the breast cancer tumor microenvironment (TME) is still poorly understood. Since there is mounting interest in the use of immunotherapy for the treatment of subsets of breast cancer patients, it is of major importance to understand the fundamental tumor characteristics which dictate the inter-tumor heterogeneity in immune landscapes. We aimed to assess the impact of EMT-related markers on the nature and magnitude of the inflammatory infiltrate present in breast cancer TME and their association with the clinicopathological parameters.

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Breast cancer is a heterogeneous disease comprising the estrogen receptor (ER)-positive luminal subtype which is subdivided into luminal A and luminal B and ER-negative breast cancer which includes the triple-negative subtype. This study has four aims: 1) to examine whether Minichromosome Maintenance (MCM)2, MCM4, and MCM6 can be used as markers to differentiate between luminal A and luminal B subtypes; 2) to study whether MCM2, MCM4, and MCM6 are highly expressed in triple-negative breast cancer, as there is an urgent need to search for surrogate markers in this aggressive subtype, for drug development purposes; 3) to compare the prognostic values of these markers in predicting relapse-free survival; and 4) to compare the three approaches used for scoring the protein expression of these markers by immunohistochemistry (IHC). MCM2, MCM4, MCM6, and MKI67 mRNA expression was first studied using in silico analysis of available breast cancer datasets.

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Interaction between immune-inflammatory process and genetic factors might be implicated in the pathogenesis of febrile seizures. Pre-microRNA (miR)-146a rs2910164 polymorphism is postulated to modulate expression of miR-146a whose anti-inflammatory role involves regulation of high-mobility group box 1. Our aim is to examine whether rs2910164 polymorphism influences serum high-mobility group box 1 levels and whether an association exists between both and febrile seizures.

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Background And Objectives: Systemic-onset juvenile idiopathic arthritis (SoJIA) is a chronic auto-inflammatory disease of childhood, with a complex genetic trait, which is characterized by arthritis associated with systemic manifestations. Familial Mediterranean fever (FMF) is another auto-inflammatory disorder that is monogenic. There are speculations as to whether Mediterranean fever (MEFV) mutations are among the genetic determinants of SoJIA.

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Background And Objectives: Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT).

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Objectives: This study aimed to evaluate the agreement between blood spot and plasma chitotriosidase using the economic substrate 4-methylumbelliferyl-β-D-N,N',N"-triacetylchitotrioside, and to investigate the utility of the blood spot assay for the wide scale screening for lysosomal storage disorders among the clinically suspected.

Design And Methods: Blinded blood spot samples were compared with the corresponding plasma levels in 199 children (56 with confirmed diagnoses of ten different lysosomal storage disorders, 73 normal controls and 70 pathological controls). Several performance criteria (limit of detection, linearity, within-run and day-to-day precision and sample stability) were also evaluated.

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Background: Atherosclerotic vascular disease represents a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD). The endothelium plays a crucial role in vascular inflammation. E-selectin is exclusively expressed on activated endothelial cells and is upregulated following an inflammatory response and oxidative stress, while serum pregnancy-associated plasma protein-A (PAPP-A) concentrations are related to the presence and stability of carotid atherosclerotic plaques.

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Background: There is considerable inter-individual variability in warfarin dosages necessary to achieve target therapeutic anticoagulation. Polymorphisms in genes, which master warfarin pharmacokinetics and pharmacodynamics, might influence warfarin dose variation. Genes encoding drug transporters, such as human multidrug resistance (MDR1), as well as epoxide hydrolase 1 (EPHX1), which is a putative subunit of the vitamin K epoxide reductase, and Protein Z (PZ), which is a vitamin K-dependent plasma glycoprotein, are among those candidate genes.

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Background: Warfarin is the most frequently prescribed oral anticoagulant worldwide. Due to its narrow therapeutic index and inter-patient variability in dose requirement, this drug has been considered an ideal target for personalised medicine. Several warfarin dosing algorithms have been proposed to tailor the warfarin dosage in the European, Asian and African-American populations.

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Background: Statins are among the most prescribed drugs worldwide to reduce the risk of cardiovascular events. Interindividual variability in drug response is a major clinical problem and is of concern during drug development. Statins, such as atorvastatin, are taken orally and access to their site of action in the liver is greatly facilitated by both intestinal and hepatic transporters.

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