ABSTRACT
This JAMA Pediatrics Patient Page describes peanut allergy guidelines and the importance of giving peanut protein to young children to prevent development of an allergy.
Subject(s)
Parents , Peanut Hypersensitivity , Humans , Peanut Hypersensitivity/prevention & control , Parents/psychology , ChildABSTRACT
This JAMA Pediatrics Patient Page describes why it is important for children to see their pediatrician for any concern about a reaction to penicillin before a child is considered to have a penicillin allergy.
Subject(s)
Drug Hypersensitivity , Hypersensitivity , Humans , Penicillins/adverse effects , Drug Hypersensitivity/diagnosis , Drug Hypersensitivity/etiology , Drug Hypersensitivity/drug therapy , Parents , Anti-Bacterial Agents/adverse effectsABSTRACT
Colorectal cancer (CRC) is the third leading cause of cancer death worldwide. It is also the third most common cancer diagnosis among men, and the second most common cancer diagnosis among women. Globally, CRC can account for nearly 694,000 annual deaths. It is widely appreciated that CRC is the result of dysregulated cellular pathways that promote an inappropriate stem-cell-like phenotype, apoptotic resistance, unchecked proliferation and metastatic spread. While no single pathway is responsible for all of these attributes, an array of recent studies suggests a pivotal role for abnormal Notch-1 signaling in CRC, in part due to interconnectivity of Notch with other pathways. This review will summarize recent evidence for a role of Notch signaling in CRC, will consider interconnectivity between Notch and other pathways involved in CRC and will discuss the possible utility of targeting Notch as a CRC therapeutic.
Subject(s)
Colorectal Neoplasms/pathology , Epithelial-Mesenchymal Transition/physiology , Receptors, Notch/metabolism , Animals , Humans , Signal Transduction/physiologyABSTRACT
Colorectal cancer (CRC) is the third leading cause of cancer death in the United States, resulting in an average of 50,000 deaths per year. Surgery and combination chemotherapy comprise current treatment strategies. However, curative options are limited if surgery and chemotherapy are unsuccessful. Several studies have indicated that CRC aggressiveness and potential for metastatic spread are associated with the acquisition of stem cell like properties. The Notch-1 receptor and its cognate signaling pathway is well known for controlling cell fate decisions and stem-cell phenotypes. Alterations in Notch receptors and Notch signaling has been reported for some colon cancers. Herein, we examine a potential role for Notch-1 signaling in CRC. In CRC patient samples, Notch-1 expression was increased in colon tumor tissue as compared with normal colon tissue. Retroviral transduction of constitutively active Notch-1 (ICN1) into the colon tumor cell line HCT-116 resulted in increased expression of the EMT/stemness associated proteins CD44, Slug, Smad-3, and induction of Jagged-1 expression. These changes in ICN1 expressing cells were accompanied by increased migration and increased anchorage independent growth by 2.5-fold and 23%, respectively. Experiments with the pan-Notch inhibitor DAPT, and soluble Jagged-1-Fc protein provided evidence that Notch-1 signaling activates CD44, Slug, and Smad-3 via a cascade of other Notch-receptors through induction of Jagged-1 expression. These data indicate a key role for Notch signaling in the phenotype of CRC and suggest that targeting of Notch signaling may be of therapeutic value in colon cancers.
