The Yin and Yang of ERBB4: Tumor Suppressor and Oncoprotein.

ERBB4 (HER4) is a member of the ERBB family of receptor tyrosine kinases, a family that includes the epidermal growth factor receptor (EGFR/ERBB1/HER1), ERBB2 (Neu/HER2), and ERBB3 (HER3). EGFR and ERBB2 are oncoproteins and validated targets for therapeutic intervention in a variety of solid tumors. In contrast, the role that ERBB4 plays in human malignancies is ambiguous. Thus, here we review the literature regarding ERBB4 function in human malignancies. We review the mechanisms of ERBB4 signaling with an emphasis on mechanisms of signaling specificity. In the context of this signaling specificity, we discuss the hypothesis that ERBB4 appears to function as a tumor suppressor protein and as an oncoprotein. Next, we review the literature that describes the role of ERBB4 in tumors of the bladder, liver, prostate, brain, colon, stomach, lung, bone, ovary, thyroid, hematopoietic tissues, pancreas, breast, skin, head, and neck. Whenever possible, we discuss the possibility that ERBB4 mutants function as biomarkers in these tumors. Finally, we discuss the potential roles of ERBB4 mutants in the staging of human tumors and how ERBB4 function may dictate the treatment of human tumors. SIGNIFICANCE STATEMENT: This articles reviews ERBB4 function in the context of the mechanistic model that ERBB4 homodimers function as tumor suppressors, whereas ERBB4-EGFR or ERBB4-ERBB2 heterodimers act as oncogenes. Thus, this review serves as a mechanistic framework for clinicians and scientists to consider the role of ERBB4 and ERBB4 mutants in staging and treating human tumors.

First-reported pediatric cases of American ginseng anaphylaxis and allergy.

BACKGROUND: Ginseng is a perennial herb used in traditional Chinese medicine, which has become increasingly popular world-wide due to its proposed medicinal effects. There are two major species of ginseng, Panax ginseng (Korean or Asian ginseng), and Panax quinquefolius (American ginseng). Although cases of allergy due to Korean ginseng have been reported in adults, there are no reported cases of allergy to American ginseng, and no reported cases of ginseng allergy in pediatric patients. CASE PRESENTATION: We present two unique cases of pediatric patients with suspected allergic reactions to American ginseng. The first patient is a 6-year-old girl who presented to the emergency department in anaphylaxis (urticaria and respiratory symptoms) minutes after inhaling powdered American ginseng. There was evidence of sensitization to American ginseng on skin prick testing (SPT) (13 × 12 mm wheal) and evidence of allergy to American ginseng on basophil activation testing, with a dose-dependent increase in expression of CD63 on basophils in response to American ginseng extract. The second patient is a 3-year-old boy who presented with recurrent allergic conjunctivitis upon exposure to aerosolized powdered ginseng, with evidence of sensitization to American ginseng on SPT (13 × 7 mm wheal), but with no evidence of IgE-mediated allergic reaction during oral challenge with American ginseng powder. CONCLUSIONS: These cases highlight two different allergic responses to American ginseng in pediatric patients. To our knowledge, these are the first reported cases of allergy to American ginseng, in addition to the first reported cases of allergy to ginseng in pediatric patients.

Yoga in rheumatic diseases.

Yoga is a popular activity which may be well suited to some individuals with specific rheumatic disorders. Regular yoga practice can increase muscle strength and endurance, proprioception, and balance, with emphasis on movement through a full range of motion to increase flexibility and mobility. Additional beneficial elements of yoga include breathing, relaxation, body awareness, and meditation, which can reduce stress and anxiety and promote a sense of calmness, general well-being, and improved quality of life. Yoga also encourages a meditative focus, increased body awareness and mindfulness; some evidence suggests yoga may help reduce inflammatory mediators including C-reactive protein and interleukin-6. Yoga is best learned under the supervision of qualified teachers who are well informed about the potential musculoskeletal needs of each individual. Here, we briefly review the literature on yoga for healthy, musculoskeletal, and rheumatic disease populations and offer recommendations for discussing ways to begin yoga with patients.