A case of steroid-resistant cystitis as an immune-related adverse event during treatment with nivolumab for lung cancer, which was successfully treated with infliximab.

Introduction: Immune checkpoint inhibitors are widely used in various cancers as a standard treatment. However, while various immune-related adverse events related to immune checkpoint inhibitors have been reported, there are few reports of lower urinary tract symptoms. Case presentation: The patient was a 60-year-old man with primary lung cancer who was receiving long-term nivolumab therapy. He was referred to our department due to the sudden onset of glans penile pain and micturition pain. We suspected non-bacterial cystitis as an immune-related adverse event caused by nivolumab and were able to treat it by administering prednisolone. While his symptoms and findings on cystoscopy recurred during prednisolone therapy, we were able to treat him again by administering an additional dose of infliximab. Conclusion: A few reports have described cases of immune checkpoint inhibitor-induced cystitis for which prednisolone was effective. This report is the first to describe cystitis as a steroid-resistant immune-related adverse event.

Epstein-Barr virus-related diffuse large B-cell lymphoma type methotrexate-associated lymphoproliferative disorders presenting in the adrenal gland.

Introduction: Methotrexate-associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined. Case presentation: A 76-year-old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B-cell lymphoma. The final diagnosis was methotrexate-associated lymphoproliferative disorders. Conclusion: It is important to consider methotrexate-associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.

Efficient Total Synthesis of Bongkrekic Acid and Apoptosis Inhibitory Activity of Its Analogues.

Bongkrekic acid (BKA), isolated from the bacterium Burkholderia cocovenenans, is an inhibitor of adenine nucleotide translocator, which inhibits apoptosis, and is thus an important tool for the mechanistic investigation of apoptosis. An efficient total synthesis of BKA has been achieved by employing a three-component convergent strategy based on Kocienski-Julia olefination and Suzuki-Miyaura coupling. It is noteworthy that segment B has been prepared as a new doubly functionalized coupling partner, which contributes to shortening of the number of steps. Torquoselective olefination with an ynolate has also been applied for the efficient construction of an unsaturated ester. Furthermore, it is revealed that 1-methyl-2-azaadamantane N-oxyl is an excellent reagent for final oxidation to afford BKA in high yield. Based on the total synthesis, several BKA analogues were prepared for structure-activity relationship studies, which indicated that the carboxylic acid moieties were essential for the apoptosis inhibitory activity of BKA. More easily available BKA analogues with potent apoptosis inhibitory activity were also developed.

High-throughput solid-phase extraction of metal ions using an iminodiacetate chelating porous disk prepared by graft polymerization.

A chelating porous sheet for use in solid-phase extraction was prepared by radiation-induced graft polymerization and subsequent chemical modifications. An epoxy-group-containing vinyl monomer was graft-polymerized onto a porous sheet made of polyethylene. The produced epoxy group of the graft chain was converted into an iminodiacetate group. The chelating porous sheet with a density of the iminodiacetate group of 2.1 mol/kg was cut into disks 13 mm in diameter to fit an empty cylindrical cartridge with a capacity of 6 mL. Breakthrough curves using the chelating-porous-disk-packed cartridge overlapped irrespective of the flow rate of the solution ranging up to 1500 mL/h because of negligible diffusional mass-transfer resistance of the copper ions to the iminodiacetate group of the graft chain.