Exacerbation of myasthenia gravis in a patient with melanoma treated with pembrolizumab.

INTRODUCTION: While anticancer immunotherapies have traditionally focused on activation of the immune system, there is recent interest in disinhibition of the natural antitumor immune response by targeting immune checkpoints such as cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). One humanized monoclonal antibody against PD-1, pembrolizumab, was recently approved for treatment of metastatic malignant melanoma. METHODS: We report exacerbation of myasthenia gravis (MG) after treatment with pembrolizumab and provide a brief literature review. RESULTS: We describe a 75-year-old man with stable MG who experienced myasthenic crisis in the setting of pembrolizumab treatment. A concurrent azathioprine taper was a possible although unlikely contributor given the short time interval between taper and exacerbation. CONCLUSIONS: As long-term data become available regarding the adverse immune effects of novel checkpoint inhibitors, clinicians should be mindful of their risks/benefits and of possible autoimmune disease exacerbation. Muscle Nerve 54: 157-161, 2016.

Defining the pathogenesis of inflammatory and immune diseases through database mining.

Recent research in human and animal genomes, transcriptomes, proteomes, and antigen-omes has generated a large library of data and has led to the establishment of many experimental data-based searchable databases. Scientists now face new, unprecedented challenges to develop more systemic methods to analyze experimental data and generate new hypotheses. This review will briefly summarize our pioneering efforts in using new database mining methods to answer important questions in inflammatory and immune-related diseases. The new principles and basic methodologies of database mining developed in Dr. Yang's laboratory will be delineated in the following studies: 1) a stimulation-responsive alternative splicing model for generating untolerized autoantigen epitopes; 2) a three-tier model for caspase-1 activation and inflammation privileges of various organs; and 3) a group of anti-inflammatory microRNAs which inhibit proatherogenic gene expression during atherogenesis. With technological advances, database mining has provided important insight into new directions for experimental research.

Homocysteine-impaired angiogenesis is associated with VEGF/VEGFR inhibition.

This study investigated the effects of homocysteine (Hcy) on angiogenesis in cultured human umbilical vein endothelial cells (HUVEC) and zebrafish embryos. We found that Hcy (50 micromol/L) significantly decreased cell numbers, viability, and induced a G1/S arrest in HUVEC in the presence of adenosine (Ade, 50 micromol/L). Hcy, in combination with Ade, reduced migration and suppressed tube-like formation on Matrigel in HUVEC. Further, Hcy reduced subintestinal vessel formation in zebrafish embryos. Interestingly, Hcy-induced inhibitory effects on cell growth, migration, tube-like formation, and vessel formation in HUVEC and zebra fish embryos were abolished by the supplement of recombinant VEGF (10 ng/ml). Finally, Hcy in combination with Ade reduced the mRNA levels of VEGF, VEGFR-1, VEGFR-2, and attenuated protein levels of VEGF, ERK1/2 and Akt. The present study suggests that Hcy inhibits angiogenesis, and that the mechanism anti-angiogenic effects of Hcy may be through VEGF/VEGFR, Akt, and ERK1/2 inhibition.