Case report of selumetinib as a novel therapy in a neurofibromatosis type 2-associated ependymoma.

We report partial response (PR) to novel therapy with selumetinib in a patient with neurofibromatosis type 2 (NF2). A 25-year-old male presented with bilateral vestibular schwannomas, spinal cord intramedullary ependymomas, cranial and spinal meningiomas, spinal nerve root mixed schwannoma-neurofibromas, and peripheral nerve sheath tumors. He tested negative for germline NF2, SWItch/sucrose non-fermentable-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1), and leucine zipper-like transcription regulator 1 (LZTR1) mutations. Molecular analysis of a resected cervical spine schwannoma-neurofibroma demonstrated an isolated somatic SMARCB1 mutation. Due to progression of all tumors, he was treated medically with both everolimus (10 mg/day) and selumetinib (25 mg/kg twice a day), but he rapidly transitioned to selumetinib monotherapy due to everolimus toxicity. 3 months of treatment resulted in PR in one spinal ependymoma and stable disease in other tumors. This PR was quantified by the differences in units of intensity in pre- and post-treatment magnetic resonance image. To the best of our knowledge, this is the first reported case for using selumetinib in NF2-associated tumors or ependymomas.

Improving Donor Livers by Inhibiting TNF-α Production.

Hepatic ischemia/reperfusion (I/R) injury has a significant influence on the outcome of liver transplants. Inhibiting certain enzymatic reactions that occur during I/R injury may have a protective effect on the liver during transplantation. After reviewing the biochemical pathways involved in hepatic I/R injury, we describe a pharmacologic line of defense against this injury by means of the enzyme tissue inhibitor of metalloproteinase 3 (TIMP-3). Current results suggest that TIMP-3 will play a clinically relevant role in improving outcomes of liver transplants by reducing I/R injury to the donor liver.