Pyoderma gangrenosum after breast cancer resection: A less-invasive and early treatment using the skin around ulcers

Surgical invasion is a risk factor of pyoderma gangrenosum (PG). A total of 25% of postoperative PG cases were reported to occur after breast surgeries, including bilateral breast reduction and breast reconstruction following cancer resection. Immunosuppressive therapy and less-invasive wound therapy are necessary; however, the complete healing of ulcers takes 5.1 months on average. We herein report a case of skin grafting under a surgical concept of less-invasive and short-term treatment. An 82-year-old woman complained of a high fever and severe pain at her breast wounds after bilateral breast cancer resection. Although we performed emergency debridement surgery to remove the necrotic tissue, suspecting surgical site infection and inflammation, her high fever persisted. She was diagnosed with PG because of the physical findings of characteristic painful, sterile ulcerations, bullae and pustules, and the pathological abundance of neutrophils in the absence of infection and vasculitis. Oral administration of prednisolone 30 mg/day improved the symptoms, and we applied negative-pressure wound therapy (NPWT) from day 16 following debridement surgery. After the gradual reduction of oral steroid intake to 12.5 mg/day, we performed skin grafting surgery. To limit the surgical invasion, we used the surplus skin around the ulcers. Split-thickness mesh skin grafts were fixed by NPWT to avoid the use of tie-over sutures. We achieved short-term treatment of PG with a less-invasive surgical strategy using skin around the ulcers and NPWT

Identification of Antigenic Site Within hsc 70 by Serum Autoantibody in Patients with Cancer-associated Retinopathy

In our previous studies, both recoverin and heat shock cognate protein 70 (hsc 70) were found as autoantigens recognized by sera from four patients with cancer-associated retinopathy (CAR) . In the present study on the mole-cular mechanism of antibody generation in CAR, we identified the antigenic site within hsc 70 by the patients\u27 sera using deletion mutants of hsc 73. We expressed a series of deletion mutants of hsc 73 proteins and subjected then to western blot analysis. In western blot analysis, CAR patient\u27s serum reacted with wild type hsp 70, but not with the C-terminal truncated mutants. This data demonstrated that the antigenic site was located within the C-terminus region of hsc 73 as identified by CAR patient\u27s serum

RUNX1 transactivates BCR-ABL1 expression in Philadelphia chromosome positive acute lymphoblastic leukemia

The emergence of tyrosine kinase inhibitors as part of a front-line treatment has greatly improved the clinical outcome of the patients with Ph⁺ acute lymphoblastic leukemia (ALL). However, a portion of them still become refractory to the therapy mainly through acquiring mutations in the BCR-ABL1 gene, necessitating a novel strategy to treat tyrosine kinase inhibitor (TKI)-resistant Ph⁺ ALL cases. In this report, we show evidence that RUNX1 transcription factor stringently controls the expression of BCR-ABL1, which can strategically be targeted by our novel RUNX inhibitor, Chb-M'. Through a series of in vitro experiments, we identified that RUNX1 binds to the promoter of BCR and directly transactivates BCR-ABL1 expression in Ph⁺ ALL cell lines. These cells showed significantly reduced expression of BCR-ABL1 with suppressed proliferation upon RUNX1 knockdown. Moreover, treatment with Chb-M' consistently downregulated the expression of BCR-ABL1 in these cells and this drug was highly effective even in an imatinib-resistant Ph⁺ ALL cell line. In good agreement with these findings, forced expression of BCR-ABL1 in these cells conferred relative resistance to Chb-M'. In addition, in vivo experiments with the Ph⁺ ALL patient-derived xenograft cells showed similar results. In summary, targeting RUNX1 therapeutically in Ph⁺ ALL cells may lead to overcoming TKI resistance through the transcriptional regulation of BCR-ABL1. Chb-M' could be a novel drug for patients with TKI-resistant refractory Ph⁺ ALL

Chlamydia trachomatis serovar L2 infection model using human lymphoid Jurkat cells

Chlamydia trachomatis L2 invasively attacks lymphatic and subepithelial tissues of the genital tract during the formation of primary lesions. This subsequently results in lymphadenopathy, and suggests a greater propensity for systemic dissemination. However, whether lymphocytes are a potential vehicle cell for the dissemination of this infection remains unknown. We therefore assessed the growth properties of C. trachomatis L2 in lymphoid Jurkat cells compared with those observed in epithelial HeLa cells. Both cells supported the growth of C. trachomatis with a similar increase in infective progenies. Enriched human-blood lymphocytes also supported the C. trachomatis growth as well as Jurkat cells. Bacteria infecting the Jurkat cells were more susceptible to antibiotics (doxycycline, azithromycin, ofloxacin) than those in HeLa cells. Of the sphingomyelin biosynthesis inhibitors tested, both myriocin and fumonisin B1 significantly inhibited bacterial growth in both cells types. A Jurkat cell mutant that impaired bacterial growth was established using ethylmethanesulfonate treatment. DNA microarray analysis with real-time reverse transcription-polymerase chain reaction revealed that the mutant cells over-expressed granzyme K gene. Immunofluorescence staining also indicated that granzyme K irregularly over-expressed among the mutant cells as compared with that of the wild cells, suggesting a possible mechanism refractory to C. trachomatis infection. Thus, we concluded that C. trachomatis L2 could infect Jurkat cells with lymphoid properties, providing a new tool for studying C. trachomatis dissemination to tissues via lymphocyte movement