Genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate in patients with rheumatoid arthritis: a multicenter cohort study.

The objective of the study is to develop genetic and clinical prediction models for the efficacy and hepatotoxicity of methotrexate (MTX) in patients with rheumatoid arthritis (RA). Among RA patients treated with MTX, 1966 polymorphisms of 246 enzymes/transporters relevant to pharmacokinetics and pharmacodynamics were measured by the Drug Metabolism Enzymes and Transporters (DMET) microarray and direct sequencing, and clinical variables at baseline were collected. For efficacy, response criteria of the European League Against Rheumatism were used to classify patients as responders or non-responders.

S100A12 facilitates osteoclast differentiation from human monocytes.

Osteoclasts play a critical role not only in bone homeostasis but also in inflammatory osteolysis, such as that occurring in inflammatory arthritis and systemic inflammation. In both inflammation conditions, inflammatory cytokines like Interleukin (IL)-1, IL-6 and tumor necrosis factor (TNF)-α induce RANKL expression in osteoblasts, but the roles of these cytokines in osteoclast activation remain unclear. S100A12, an S100 family member, is a low-molecular-weight calcium-binding protein.

[Current situation and challenges in companion diagnostics development].

The personalized health care, it is defined as a medical care which provide the optimal therapy for each individual in consideration of a patient's individual difference, such as a genetic background and a physiological state. A companion diagnosis to stratify a patient appropriately is essential for the spread of personalized health care, and it is important that a companion diagnostic reagent used for the companion diagnosis is properly developed and clinically applied. However, as for the development of companion diagnostics and pharmaceuticals that require it, there are still many challenges such as its business model of cooperation of diagnostics companies and pharmaceutical companies, also, the regulations related to companion diagnostics.

The usefulness of immunohistochemical evaluation of dihydropyrimidine dehydrogenase for rectal cancer treated with preoperative radiotherapy.

Background/aims: DPD (dihydropyrimidine dehydrogenase) activity shows a correlation with 5-fluorouracil chemosensitivity. To quantify DPD activity is important for selection of chemosensitive cases of not only sporadic colorectal cancer but also rectal cancer with preoperative radiotherapy. However, it is not cost-effective.