A case of erythema multiforme-like rash induced by everolimus in a patient with a pancreatic neuroendocrine tumor.

A 66-year-old Japanese woman had been diagnosed with a neuroendocrine tumor of the pancreatic head (G2) 3 years previously and undergone pancreaticoduodenectomy. Nine months postoperatively, recurrence with multiple liver metastases developed and she was referred to our department. A regimen of 10 mg of everolimus for 2 weeks plus 1-week washout was instituted, and no adverse events were observed. Fourteen months after treatment initiation, she developed severe generalized erythema multiforme (EM). Skin biopsy revealed spongiosis in the epidermis and interface change and edema in the superficial dermis. Mast cells were observed from the dermis to the subcutaneous tissue, as well as perivascular eosinophilic infiltration, leading to EM being diagnosed. Oral everolimus was discontinued, and the EM was relieved by treatment including steroid therapy. Everolimus is an inhibitor of the mammalian target of rapamycin, and its indications include neuroendocrine tumors. Skin disorders are commonly seen in the early stages of everolimus treatment, but their severity is almost always mild and never severe. This is the first report on a patient who presented with severe generalized EM more than 1 year after everolimus treatment initiation. Patients on everolimus therapy should be monitored for skin disorders on a long-term basis.

Influence of Culture Period on Osteoblast Differentiation of Tissue-Engineered Bone Constructed by Apatite-Fiber Scaffolds Using Radial-Flow Bioreactor.

With the limitation of autografts, the development of alternative treatments for bone diseases to alleviate autograft-related complications is highly demanded. In this study, a tissue-engineered bone was formed by culturing rat bone marrow cells (RBMCs) onto porous apatite-fiber scaffolds (AFSs) with three-dimensional (3D) interconnected pores using a radial-flow bioreactor (RFB). Using the optimized flow rate, the effect of different culturing periods on the development of tissue-engineered bone was investigated. The 3D cell culture using RFB was performed for 0, 1 or 2 weeks in a standard medium followed by 0, 1 or 2 weeks in a differentiation medium. Osteoblast differentiation in the tissue-engineered bone was examined by alkaline phosphatase (ALP) and osteocalcin (OC) assays. Furthermore, the tissue-engineered bone was histologically examined by hematoxylin and eosin and alizarin red S stains. We found that the ALP activity and OC content of calcified cells tended to increase with the culture period, and the differentiation of tissue-engineered bone could be controlled by varying the culture period. In addition, the employment of RFB and AFSs provided a favorable 3D environment for cell growth and differentiation. Overall, these results provide valuable insights into the design of tissue-engineered bone for clinical applications.

Rapid and easy method for in vitro determination of transcription factor binding core motifs.

We introduce a rapid method for easily elucidating transcription factor (TF) cis-elements by adopting a highly efficient in vitro protein synthesis method and identifying protein-DNA interactions using PCR. We determined two cis-elements for plant TFs using this method, and the results confirmed our method as an easy and time-saving alternative for elucidating TF cis-elements using common laboratory procedures.