RESUMO
During routine dissection of 11 cadavers that originated with the Body Donor Program at Philadelphia College of Osteopathic Medicine (PCOM) Georgia, a 69-year-old African American male with bilateral extensor anomalies in the dorsal forearm compartment was encountered. The distinct muscle belly, identified as the extensor medii proprius (EMP), originated from the distal ulna and was inserted near the dorsal aponeurosis of the third digit. Manual traction of the right EMP tendon resulted in the extension of the third digit, suggesting the functional significance of the anomalous muscle. This case study analyzes the EMP found during dissection, as well as the anomalous muscle's prevalence, embryologic origin, and clinical relevance. The presence of the EMP muscle and tendon can be considered when assessing pain in the dorsum of the hand and when preparing for surgical repair or tendon transfer.
RESUMO
Neurofibromatosis type 2 (NF2) is a genetic syndrome that predisposes individuals to multiple benign tumors of the central and peripheral nervous systems, including vestibular schwannomas. Currently, there are no FDA approved drug therapies for NF2. Loss of function of merlin encoded by the NF2 tumor suppressor gene leads to activation of multiple mitogenic signaling cascades, including platelet-derived growth factor receptor (PDGFR) and SRC in Schwann cells. The goal of this study was to determine whether ponatinib, an FDA-approved ABL/SRC inhibitor, reduced proliferation and/or survival of merlin-deficient human Schwann cells (HSC). Merlin-deficient HSC had higher levels of phosphorylated PDGFRα/ß, and SRC than merlin-expressing HSC. A similar phosphorylation pattern was observed in phospho-protein arrays of human vestibular schwannoma samples compared to normal HSC. Ponatinib reduced merlin-deficient HSC viability in a dose-dependent manner by decreasing phosphorylation of PDGFRα/ß, AKT, p70S6K, MEK1/2, ERK1/2 and STAT3. These changes were associated with decreased cyclin D1 and increased p27Kip1levels, leading to a G1 cell-cycle arrest as assessed by Western blotting and flow cytometry. Ponatinib did not modulate ABL, SRC, focal adhesion kinase (FAK), or paxillin phosphorylation levels. These results suggest that ponatinib is a potential therapeutic agent for NF2-associated schwannomas and warrants further in vivo investigation.
