Treatment-related leukoencephalopathy in adults with central nervous system lymphoma: a retrospective analysis of 126 patients.

Neurotoxicity associated with high-dose chemotherapy and whole brain radiotherapy (WBRT) is one of major complications for patients with central nervous system lymphoma (CNSL). Here we determined the incidence and risk factors of treatment-related leukoencephalopathy (tLE) in a clinical setting. We retrospectively reviewed clinical and radiological findings of 126 patients with  (CNSL) treated with high-dose methotrexate with or without intrathecal methotrexate administration (IT MTX) and response-adapted WBRT. During the whole observation period with a median of 38.7 months, tLE was found in 33 patients, most of them asymptomatic, with the median time to development 3.0 months, and the cumulative incidence reaching 29.2% (95% confidence interval, 20.6-38.2%) two years post chemotherapy. By multivariable analysis, IT MTX was identified as the only one significant risk factor (hazard ratio, 4.50; P < 0.001), and the number of IT MTX was associated with the increased incidence and severity of tLE. These findings highlight the frequent neurological complications associated with CNS-directed therapy and confirm the neurotoxicity of IT MTX.

Hybrid molecule between platanic acid and LCL-161 as a yes-associated protein degrader.

Dysregulated yes-associated protein (YAP) is involved in several malignant cancers. However, discovering a druggable YAP inhibitor(s) is difficult because YAP itself does not have any enzymatic activity. In such cases, targeted protein degradation strategies based on hybrid molecules that bind to the target protein and an E3 ubiquitin ligase are useful for suppressing proteins that exhibit aberrant activation and/or excessive expression. Upon screening YAP-interacting small compounds, we identified HK13, a platanic acid, as a novel compound that interacts with YAP. Next, we synthesized hybrid compounds of platanic acid and LCL-161, which reportedly shows a high affinity for cIAP, one of E3 ubiquitin ligases. Among these compounds, HK24 possessed the ability to inhibit the growth of YAP overexpressing NCI-H290 cells. This inhibitory activity may be mediated by YAP degradation, although HK24 exhibited weak YAP degradation. Furthermore, we confirmed involvement of proteasome pathway in HK24-dependent YAP degradation by culturing NCI-H290 cells in the presence of a proteasome inhibitor. Therefore, it is possible that platanic acid is a potential candidate for molecular medicine targeting YAP.

Genetic relationship of Corynebacterium diphteriae strains isolated from diphteria case and carriers by restriction fragment length polymorphism of rRNA genes

No presente estudo, nos reportamos os resultados de uma analise, baseada na ribotipagem de cepas de C. diphtheriae intermedius isoladas de uma crianca de 9 anos com difteria e seus 5 contatos. Analise quantitativa por RFLP de rRNA foi usada para determinar a relacao destas 7 cepas de C.diphtheriae fornecendo dados de interesse epidemiologico...