Translational research : the journal of laboratory and clinical medicine
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Functional studies of long noncoding RNAs (lncRNAs) are often performed in the context of only a single cancer type. However, the tissue-specific expression patterns of lncRNAs raise the question of whether lncRNA associations identified in one cancer type are relevant to other cancer types. Here, we examine the relationships between the expression levels of 50 cancer-related lncRNAs and survival data from 24 types of cancer in The Cancer Genome Atlas (TCGA) with the goal of identifying prognosis related lncRNAs. ⋯ In addition, in low-grade glioma (LGG), prognostic-related lncRNAs are identified after conditioning on known clinical biomarker and common therapy, revealing that 2 lncRNAs, FOXP4-AS1, and NEAT1, are associated with temozolomide response-a standard-of-care in LGG. Pathway analysis suggests NF-kB/STAT3 signaling pathway enrichment in LGG patients with high NEAT1 expression and DNA repair/myc gene set enrichment in LGG patients with high expression of FOXP4-AS1. Our work demonstrates the context dependency of lncRNAs across cancer types and highlights a number of lncRNAs as potential novel cancer prognosis markers.
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Loss of hepatocellular carcinoma-related protein 1 (HCRP1) (alias VPS37A) plays a role in endocytosis of receptor tyrosine kinases as a member of the ESCRT complex and has been linked to poor patient outcome in various types of epithelial cancer. To this date, the molecular and biological mechanisms explaining how its absence would contribute to tumor progression remain unknown. Using genomic editing with CRISPR-Cas9, we generated ovarian and breast cancer cell lines with loss-of-function mutations of HCRP1. ⋯ In our study, we show that endogenous deletion of HCRP1 leads to elevated phosphorylation of the transcription factor Signal transducer and activator of transcription 3 (STAT3) and induces upregulation of PD-L1, an important regulator of immune checkpoint inhibition. HCRP1 loss further leads to a mesenchymal phenotype switch in cancer cells, leading to increased proliferation and migration. Concludingly, our data emphasize the role of the tumor microenvironment in tumors with low or absent HCRP1 expression and suggest HCRP1 loss as a potential marker for metastatic potential and immunogenicity of epidermal growth factor receptor-driven cancer.
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In our study, we treated high fructose diet-induced insulin resistance in rats with any of metformin, cabbage (80%w/w) or combined metformin and cabbage (MetCabb), and observed the activities of glycolysis and gluconeogenesis regulatory enzymes, incretin hormones and other hormones affecting glucose homeostasis. Comparisons were made with normoglycemic noninsulin resistance rats (control) and insulin-resistant untreated rats (INres). Baseline analysis showing elevated fasting blood sugar (>250 mg/dl), insulin (>25 µIU/ml) and HOMA-IR (>10) satisfied the criteria for recruitment into the insulin-resistant groups. ⋯ The hexokinase (r = -0.807), PFK (r = -0.9151), and PK (r = -0.7448) levels regressed as HOMA-IR values increased. The glycolytic and gluconeogenic enzymes except PEPCK reverted to control levels with MetCabb treatment. Combination of metformin and cabbage was more effective than individual treatments.
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Cardiac autonomic imbalance including sympathetic overactivity and diminished parasympathetic activity is associated with left ventricular (LV) dysfunction in cases of cardiac ischemia/reperfusion (I/R) injury. Electrical stimulation to increase vagal activity has been shown to reduce infarct size and decrease fatal arrhythmias in cardiac I/R injury. However, the benefits of a parasympathomimetic drug on the heart during I/R are unclear. ⋯ Rats with cardiac I/R injury showed an increase in infarct size and arrhythmia score, LV dysfunction, impaired mitochondrial dynamic balance, autophagy and mitophagy, mitochondrial dysfunction, and increased apoptosis. All the donepezil-treated rats, regardless of the time of administration, showed a similar reduction in these impairments, and rebalancing in cardiac mitochondrial dynamics, leading to reduced myocardial infarct size and arrhythmia, and improved LV function. These findings suggested that donepezil effectively protected the heart against I/R injury through cardiac mitochondrial protection regardless of the time of administration.
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Case Reports
Trehalose as quantitative biomarker for in vivo diagnosis and treatment follow-up in cryptococcomas.
Brain lesions caused by Cryptococcus neoformans or C. gattii (cryptococcomas) are typically difficult to diagnose correctly and treat effectively, but rapid differential diagnosis and treatment initiation are crucial for good outcomes. In previous studies, cultured cryptococcal isolates and ex vivo lesion material contained high concentrations of the virulence factor and fungal metabolite trehalose. Here, we studied the in vivo metabolic profile of cryptococcomas in the brain using magnetic resonance spectroscopy (MRS) and assessed the relationship between trehalose concentration, fungal burden, and treatment response in order to validate its suitability as marker for early and noninvasive diagnosis and its potential to monitor treatment in vivo. ⋯ Trehalose concentrations correlated strongly with the fungal burden. Treatment studies in cultures and animal models showed that trehalose concentrations decrease following exposure to effective antifungal therapy. Although further cases need to be studied for clinical validation, this translational study indicates that the noninvasive MRS-based detection of trehalose is a promising marker for diagnosis and therapeutic follow-up of cryptococcomas.