Aberrant methylation of promoter CpG islands (CGI) is involved in silencing of tumor suppressor genes and is also a potential cancer biomarker. Here, to identify CGIs aberrantly methylated in human melanomas, we did a genomewide search using methylation-sensitive representational difference analysis. CGIs in putative promoter regions of 34 genes (ABHD9,

Clinically, patients' adherence to biologic treatment is not only related to efficacy but also to adverse events, cost and other factors. To evaluate long-term viability of biologic treatment, both the percentage of and reasons for discontinuation of treatment were investigated. In this study, patients treated with infliximab (n = 38), adalimumab (n = 59) and ustekinumab (n = 30) were included and observed for 12 months. Clinical efficacy was evaluated using a 75% reduction of Psoriasis Area and Severity Index score (PASI-75), and patients who discontinued treatment were considered as not having achieved PASI-75. In addition, drug survival rate (DSR) was investigated. In patients treated with infliximab, PASI-75 was 68.4% and DSR was 73.3% by the end of treatment. In patients treated with adalimumab, PASI-75 was 50.8% and DSR was 79.7%. In patients treated with ustekinumab, PASI-75 was 63.3% and DSR was 96.7%. Several patients discontinued treatment because of insufficient efficacy due to secondary failure in infliximab or primary failure in adalimumab. To increase treatment efficacy, it will be necessary for these patients to use an additional concomitant treatment. Higher efficacy is expected with biologics than with conventional treatments; however, the actual clinical efficacy over a long period of time may be insufficient if they are used without any concomitant treatments.

Tumor suppressors with extracellular function are likely to have advantages as targets for cancer therapy, but few are known. Here, we focused on angiopoietin-like 4 (ANGPTL4), which is a secreted glycoprotein involved in lipoprotein metabolism and angiogenesis, is methylation-silenced in human cancers, but has unclear roles in cancer development and progression. We found a deletion mutation in its coiled-coil domain at its N-terminal in human gastric cancers, in addition to hypermethylation of the ANGPTL4 promoter CpG islands. Forced expression of wild-type ANGPTL4, but not ANGPTL4 with the deletion, at physiological levels markedly suppressed in vivo tumorigenicity and tumor angiogenesis, indicating that the latter caused the former. Tumor-derived ANGPTL4 suppressed in vitro vascular tube formation and proliferation of human umbilical vascular endothelial cells, partly due to suppression of ERK signaling. These showed that ANGPTL4 is a genetically and epigenetically inactivated secreted tumor suppressor that inhibits tumor angiogenesis.

We report a case of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) in a 21-year-old man. This disease is a severe form of pityriasis lichenoides et varioliformis acuta (PLEVA) and is characterized by the sudden onset of diffuse ulcerations associated with high fever and systemic symptoms. It is sometimes lethal especially in elderly patients. In the present case, intense generalized maculopapular erythematous plaques with central necrosis developed progressively in association with a high fever. Initial treatment with systemic betamethasone had been unsuccessful and the skin lesions, which covered about 50% of the body surface, became severely ulcerated. Although the development of new lesions had ceased spontaneously, widespread ulceration of the skin remained. Debridement of the necrotic skin and skin grafting using cultured epidermal autografts and meshed allografts of cadaver skin led to prompt reepithelization.

Efficacy and safety profiles of biologics have been established for moderate to severe psoriasis. However, inefficacy or adverse events sometimes require changing the treatment to other biologics. Here, we examine the effectiveness of this strategy. We retrospectively investigated cases requiring switching biologics. We enrolled 275 psoriatic patients treated with biologics between January 2010 and December 2014 in our hospital. Of these, 51 required a switch to another biologic. First-line therapies were infliximab (IFX, n = 26), adalimumab (ADA, n = 18) and ustekinumab (UST, n = 7), and second-line therapies were IFX (n = 5), ADA (n = 21) and UST (n = 25). Reasons for switching were inefficacy (n = 38), adverse events (n = 11) and others (n = 2). The details were primary failure (n = 15), secondary failure (n = 23) and infusion reactions (n = 8). In 49 patients who switched biologics due to inefficacy and adverse events, the mean Psoriasis Area and Severity Index (PASI) score at week 16 was 4.3 for first-line therapies and 2.9 for second-line therapies (P < 0.05). Switching to a second biologic therapy to address the first's inefficacy or adverse events often results in significant improvement in moderate to severe psoriasis.