Breast cancer anti-estrogen resistance 3 (BCAR3) protein augments binding of the c-Src SH3 domain to Crk-associated substrate (p130cas).

The focal adhesion adapter protein p130(cas) regulates adhesion and growth factor-related signaling, in part through Src-mediated tyrosine phosphorylation of p130(cas). AND-34/BCAR3, one of three NSP family members, binds the p130(cas) carboxyl terminus, adjacent to a bipartite p130(cas) Src-binding domain (SBD) and induces anti-estrogen resistance in breast cancer cell lines as well as phosphorylation of p130(cas). Only a subset of the signaling properties of BCAR3, specifically augmented motility, are dependent upon formation of the BCAR3-p130(cas) complex. Using GST pull-down and immunoprecipitation studies, we show that among NSP family members, only BCAR3 augments the ability of p130(cas) to bind the Src SH3 domain through an RPLPSPP motif in the p130(cas) SBD. Although our prior work identified phosphorylation of the serine within the p130(cas) RPLPSPP motif, mutation of this residue to alanine or glutamic acid did not alter BCAR3-induced Src SH3 domain binding to p130(cas). The ability of BCAR3 to augment Src SH3 binding requires formation of a BCAR3-p130(cas) complex because mutations that reduce association between these two proteins block augmentation of Src SH3 domain binding. Similarly, in MCF-7 cells, BCAR3-induced tyrosine phosphorylation of the p130(cas) substrate domain, previously shown to be Src-dependent, was reduced by an R743A mutation that blocks BCAR3 association with p130(cas). Immunofluorescence studies demonstrate that BCAR3 expression alters the intracellular location of both p130(cas) and Src and that all three proteins co-localize. Our work suggests that BCAR3 expression may regulate Src signaling in a BCAR3-p130(cas) complex-dependent fashion by altering the ability of the Src SH3 domain to bind the p130(cas) SBD.

Systemic Steroids for Otolaryngology-Head and Neck Surgery Disorders: An Evidence-Based Primer for Clinicians.

OBJECTIVE: To offer pragmatic, evidence-informed guidance on the use of systemic corticosteroids (SCS) for common otolaryngologic disorders. DATA SOURCES: PubMed, Cochrane Library, and American Academy of Otolaryngology-Head and Neck Surgery Foundation clinical practice guidelines. REVIEW METHODS: A comprehensive search of published literature through November 2021 was conducted on the efficacy of SCS, alone or in combination with other treatments, for managing disorders in otolaryngology and the subdisciplines. Clinical practice guidelines, systematic reviews, and randomized controlled trials, when available, were preferentially retrieved. Interventions and outcomes of SCS use were compiled to generate summary tables and narrative synthesis of findings. CONCLUSIONS: Evidence on the effectiveness of SCS varies widely across otolaryngology disorders. High-level evidence supports SCS use for Bell's palsy, sinonasal polyposis, and lower airway disease. Conversely, evidence is weak or absent for upper respiratory tract infection, eustachian tube dysfunction, benign paroxysmal positional vertigo, adenotonsillar hypertrophy, or nonallergic rhinitis. Evidence is indeterminate for acute laryngitis, acute pharyngitis, acute sinusitis, angioedema, chronic rhinosinusitis without polyps, Ménière's disease, postviral olfactory loss, postoperative nerve paresis/paralysis, facial pain, and sudden sensorineural hearing loss. IMPLICATIONS FOR PRACTICE: Clinicians should bring an evidence-informed lens to SCS prescribing to best counsel patients regarding the risks, anticipated benefits, and limited data on long-term effects. Alternate routes of corticosteroid administration-such as sprays, drops, inhalers, and intralesional injections-may be preferable for many disorders, particularly those that are self-limited or require a prolonged duration of therapy. Prudent use of SCS reduces the risk of medication-related adverse effects. Clinicians who are conversant with high-level evidence can achieve optimal outcomes and stewardship when prescribing SCS.

Upper lip frenotomy for neonatal breastfeeding problems.

OBJECTIVES: Upper lip tie, without concomitant tongue tie, can prevent proper flanging of the upper lip during breastfeeding, resulting in a poor seal and suck for the infant with nipple pain and maternal dissatisfaction. Due to the lack of published studies on this subject, we report our technique and outcomes for in-office release of isolated upper lip tie. METHODS: Using CPT Code 40,806 for 'incision of labial frenulum', 22 mother-infant dyads with infant age under 60 days with breastfeeding problems and a restrictive upper lip frenum were identified. These infants underwent in-office release of upper lip tie as detailed below. Outcomes of the procedure were assessed by a telephone survey to mothers within the 4-week period post-procedure. RESULTS: 82% of mothers reported an improved latch and 73% noted increased satisfaction with breastfeeding. Lip pain, if present, resolved within 24 h for most children. Recurrence was reported by 9% of mothers; no infection or other complications occurred. CONCLUSION: Upper lip frenotomy, in properly selected infants, has favorable short-term outcomes with mild transient discomfort and a low rate of recurrence. Since our study was short-term and did not include a control group, we are unable to comment on procedure efficacy or long-term impact.