The betacoronavirus, SARS-CoV-2, that is responsible for COVID-19 disease and that was first described in Wuhan, China, in late 2019, has swiftly made its way around our world, resulting in excess of 30,000 deaths to date (1). Efforts to recognize SARS-CoV-2 infection have focused on respiratory symptoms such as cough and shortness of breath (2,3). Currently, the Centers for Disease Control and Prevention (CDC) criteria for identifying persons under investigation for SARS-CoV-2 infection in the United States comprise respiratory symptoms and/or fever only (4). Recent reports from China have described concomitant digestive symptoms, such as nausea, vomiting, diarrhea, and abdominal pain, in patients with confirmed SARS-CoV-2 pulmonary infection (5-8)
For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.
Colorectal cancer is the second leading cause of cancer mortality in the United States. Substantial human and animal data support the ability of nonsteroidal antiinflammatory drugs to cause regression of existing colon tumors and prevent new tumor formation. The mechanism by which the nonsteroidal anti-inflammatory drug sulindac prevents tumor growth is poorly understood and seems complex as sulindac can modulate several growth-related signaling pathways. Sulindac metabolites simultaneously (a) increase cellular cyclic GMP and subsequently activate cyclic GMP -dependent protein kinase (PKG); (b) activate c-jun NH 2 -terminal kinase (JNK); (c) inhibit extracellular signal -regulated kinase 1/2 (ERK1/2); and (d) decrease B-catenin protein expression at times and doses consistent with apoptosis. The purpose of this study was to determine if PKG, ERK1/2, JNK, and B-catenin are independent targets for sulindac in vitro. Pharmacologic activation of PKG with YC-1 increases JNK phosphorylation and induces apoptosis in colon cancer cells without modulating ERK1/2 phosphorylation or B-catenin protein expression. Inhibition of ERK1/2 with U0126 induces apoptosis but fails to activate JNK phosphorylation or down-regulate B-catenin protein expression. Cotreatment with U0126 and YC-1 synergistically increases apoptosis in colorectal cancer cells and recapitulates the effects of sulindac treatment on ERK1/2, JNK, and B-catenin. These results indicate that sulindac metabolites modulate ERK1/2 and PKG pathways independently in colon cancer cells and suggest that the full apoptotic effect of sulindac is mediated by more than one pathway. Using similar combinatorial approaches in vivo may provide more effective, less toxic chemopreventive and chemotherapeutic strategies. Such therapies could dramatically reduce the incidence and death rate from colorectal cancer. [Mol Cancer Ther 2006;5(3):746 -54]
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.