A B S T R A C T PurposeLung squamous cell carcinoma (SCC) is the second most prevalent type of lung cancer. Currently, no targeted therapeutics are approved for treatment of this cancer, largely because of a lack of systematic understanding of the molecular pathogenesis of the disease. To identify therapeutic targets and perform comparative analyses of lung SCC, we probed somatic genome alterations of lung SCC by using samples from Korean patients. Patients and MethodsWe performed whole-exome sequencing of DNA from 104 lung SCC samples from Korean patients and matched normal DNA. In addition, copy-number analysis and transcriptome analysis were conducted for a subset of these samples. Clinical association with cancer-specific somatic alterations was investigated. ResultsThis cancer cohort is characterized by a high mutational burden with an average of 261 somatic exonic mutations per tumor and a mutational spectrum showing a signature of exposure to cigarette smoke. Seven genes demonstrated statistical enrichment for mutation: TP53, RB1, PTEN, NFE2L2, KEAP1, MLL2, and PIK3CA). Comparative analysis between Korean and North American lung SCC samples demonstrated a similar spectrum of alterations in these two populations in contrast to the differences seen in lung adenocarcinoma. We also uncovered recurrent occurrence of therapeutically actionable FGFR3-TACC3 fusion in lung SCC. ConclusionThese findings provide new steps toward the identification of genomic target candidates for precision medicine in lung SCC, a disease with significant unmet medical needs.
Somatostatin (SST) is a well-known neuropeptide that is expressed throughout the brain. In the cortex, SST is expressed in a subset of GABAergic neurons and is known as a protein marker of inhibitory interneurons. Recent studies have identified the key functions of SST in modulating cortical circuits in the brain and cognitive function. Furthermore, reduced expression of SST is a hallmark of various neurological disorders, including Alzheimer’s disease and depression. In this review, we summarize the current knowledge on SST expression and function in the brain. In particular, we describe the physiological roles of SST-positive interneurons in the cortex. We further describe the causal relationship between pathophysiological changes in SST function and various neurological disorders, such as Alzheimer’s disease. Finally, we discuss potential treatments and possibility of novel drug developments for neurological disorders based on the current knowledge on the function of SST and SST analogs in the brain derived from experimental and clinical studies.
In modern society, growing numbers of people are engaged in various forms of shift works or trans-meridian travels. Such circadian misalignment is known to disturb endogenous diurnal rhythms, which may lead to harmful physiological consequences including metabolic syndrome, obesity, cancer, cardiovascular disorders, and gastric disorders as well as other physical and mental disorders. However, the precise mechanism(s) underlying these changes are yet unclear. The present work, therefore examined the effects of 6 h advance or delay of usual meal time on diurnal rhythmicities in home cage activity (HCA), body temperature (BT), blood metabolic markers, glucose homeostasis, and expression of genes that are involved in cholesterol homeostasis by feeding young adult male mice in a time-restrictive manner. Delay of meal time caused locomotive hyperactivity in a significant portion (42%) of subjects, while 6 h advance caused a torpor-like symptom during the late scotophase. Accordingly, daily rhythms of blood glucose and triglyceride were differentially affected by time-restrictive feeding regimen with concurrent metabolic alterations. Along with these physiological changes, time-restrictive feeding also influenced the circadian expression patterns of low density lipoprotein receptor (LDLR) as well as most LDLR regulatory factors. Strikingly, chronic advance of meal time induced insulin resistance, while chronic delay significantly elevated blood glucose levels. Taken together, our findings indicate that persistent shifts in usual meal time impact the diurnal rhythms of carbohydrate and lipid metabolisms in addition to HCA and BT, thereby posing critical implications for the health and diseases of shift workers.
AIM:To investigate the anti-cancer mechanisms of Korean mistletoe lectin (Viscum album coloratum agglutinin, VCA) using a human colon cancer cell line (COLO). METHODS:Cytotoxic effects of VCA on COLO cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay in vitro and tumor-killing effects in vivo. To study the mechanisms involved, the expression of various pro-caspases, antiapoptotic proteins, and death receptors was determined by western blot. To determine which death receptor is involved in VCA-induced apoptosis of COLO cells, cytotoxicity was examined by MTT assay after treatment with agonists or antagonists of death receptors. RESULTS:VCA killed COLO cells in a time-and dosedependent manner and induced complete regression of tumors in nude mice transplanted with COLO cells. Treatment of COLO cells with VCA activated caspase-2, -3, -8, and -9 and decreased expression of anti-apoptotic molecules including receptor interacting protein, nuclear factor-κB, X-linked inhibitor of apoptosis protein, and Akt/protein kinase B. We then examined the involvement of death receptors in VCA-induced apoptosis. Only tumor necrosis factor receptor 1, among the death receptors examined, was involved in apoptosis of COLO cells, evidenced by inhibition of VCA-induced apoptosis and decreased activation of caspases, particularly caspase-8, by tumor necrosis factor receptor 1 antagonizing antibody. CONCLUSION:VCA-induced apoptotic COLO cell death is due to the activation of caspases and inhibition of antiapoptotic proteins, in part through the tumor necrosis factor receptor 1 signaling pathway.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.