Browsing by Subject "NanoString"

Now showing 1 - 3 of 3
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    Molecular Classification of Bladder Urothelial Carcinoma Using NanoString-Based Gene Expression Analysis
    (MDPI, 2021-11-01) Lopez-Beltran, Antonio; Blanca, Ana; Cimadamore, Alessia; Gogna, Rajan; Montironi, Rodolfo; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    Molecular classification of bladder carcinoma is a relevant topic in modern bladder cancer oncology due to its potential to improve oncological outcomes. The available molecular classifications are generally based on transcriptomic profiles, generating highly diverse categories with limited correlation. Implementation of molecular classification in practice is typically limited due to the high complexity of the required technology, the elevated costs, and the limited availability of this technology worldwide. We have conducted a gene expression analysis using a four-gene panel related to luminal and basal subtypes in a series of 91 bladder cancer cases. NanoString-based gene expression analysis using typically luminal (GATA3+/KRT20+) and basal markers (KRT14+/KRT5+/GATA3low/-/KRT20low/-) classified urothelial bladder carcinoma samples as luminal, basal, and a third category (KRT14-/KRT5-/GATA3-/KRT20-), null/double negative (non-luminal/non-basal). These three categories were meaningful in terms of overall cancer-specific survival (p < 0.0001) or when classified as conventional urothelial carcinoma and variant histology urothelial carcinoma (p < 0.0001), NMIBC vs. MIBC (p < 0.001), or by AJCC stage category Ta (p = 0.0012) and T1 (p < 0.0001) but did not reach significance in T2-T4 (p = 0.563). PD-L1 expression (low vs. high) was also different according to molecular subtype, with high PD-L1 expression mostly seen in basal and null subtypes and carcinomas with variant histology (p = 0.002). Additionally, the luminal subtype was enriched in NMIBC with favorable cancer-specific survival (p < 0.0001). In contrast, basal and null subtypes resulted in aggressive MIBC tumors with shorter cancer-specific survival (p < 0.0001), some of which presented variant histology. In conclusion, a comprehensive evaluation of a gene classifier related to molecular taxonomy using NanoString technology is feasible. Therefore, it might represent an accessible and affordable tool in this rapidly expanding area of precision genomics.
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    Propranolol Elicits Long Term Systemic Effects After Repetitive Mild Traumatic Brain Injury
    (2023-07) Smith, Jared Andre; Obukhov, Alexander; White, Fletcher; Hato, Takashi; Naugle, Kelly; Jin, Xiaoming; Truitt, William; Grimes, Jaison
    There are almost 2 million new traumatic brain injuries (TBIs) every year in the US. Of these, 80% of these can be classified as mild TBI, also known as concussions, that can lead to pronounced long term symptoms months and years after injury. The presence of post traumatic headaches (PTH) is the most common chronic side effect with prevalence of 47-95% of mTBI patients within a week of injury. Though the mechanisms after TBI leading to these headaches and other post mTBI side effects are poorly understood, recent studies have suggested the role of the immune system after injury plays a causal role in this process. Peripheral immune cells can travel to the brain after mTBI as a result of blood brain barrier dysfunction, sympathetic nervous signaling, and the release of inflammatory mediators. Recent studies have shown sympathetic activation after injury can result in IL-10 dependent systemic immunosuppressive state after mTBI. In this study we sought to limit sympathetic dependent immune alterations after injury by injecting the beta blocker propranolol directly after injury and investigating the immune changes in the blood, brain, spleen, and bone marrow of mTBI animals. Together, these data show mTBI causes immune genetic and pathway level changes at least one month after injury and that propranolol alters genes important for metabolism, cytokine signaling, epigenetic modification, innate, and adaptive immunity. We also find that propranolol reduces the presence of Ly6C+ and increases the presence of Ly6C- monocytes in the blood one month after injury; however, it leads to increased Ly6C+ monocyte presence in the spleen of mTBI mice. In conclusion, propranolol administration directly after mTBI leads to immune changes that may lead to long-term improvement in post TBI symptomology.
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    Reduction in GABAB on glia induce Alzheimer's disease related changes
    (Elsevier, 2023) Leisgang Osse, Amanda M.; Pandey, Ravi S.; Wirt, Ryan A.; Ortiz, Andrew A.; Salazar, Arnold; Kimmich, Michael; Strom, Erin N.; Oblak, Adrian; Lamb, Bruce; Hyman, James M.; Carter, Gregory W.; Kinney, Jefferson; Radiology and Imaging Sciences, School of Medicine
    Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by beta-amyloid plaques (Aβ), neurofibrillary tangles (NFT), and neuroinflammation. Data have demonstrated that neuroinflammation contributes to Aβ and NFT onset and progression, indicating inflammation and glial signaling is vital to understanding AD. A previous investigation demonstrated a significant decrease of the GABAB receptor (GABABR) in APP/PS1 mice (Salazar et al., 2021). To determine if changes in GABABR restricted to glia serve a role in AD, we developed a mouse model with a reduction of GABABR restricted to macrophages, GAB/CX3ert. This model exhibits changes in gene expression and electrophysiological alterations similar to amyloid mouse models of AD. Crossing the GAB/CX3ert mouse with APP/PS1 resulted in significant increases in Aβ pathology. Our data demonstrates that decreased GABABR on macrophages leads to several changes observed in AD mouse models, as well as exacerbation of AD pathology when crossed with existing models. These data suggest a novel mechanism in AD pathogenesis.