Prospective feasibility study of neoadjuvant dose-dense paclitaxel plus carboplatin with bevacizumab therapy followed by interval debulking surgery for advanced ovarian,fallopian tube,and primary peritoneal cancer patients

International Journal of Clinical Oncology - This study aimed to investigate the clinical benefit of dose-dense paclitaxel plus carboplatin (TC) with bevacizumab therapy for advanced ovarian,...     

Expression of recombination activating genes 1 and 2 in peripheral B cells of patients with systemic lupus erythematosus

OBJECTIVE: To analyze immunoregulatory abnormalities in patients with systemic lupus erythematosus (SLE) by assessing the expression of messenger RNA (mRNA) for types 1 and 2 recombination activating genes (RAG) in the peripheral blood of patients with active SLE. METHODS: We examined B cell populations and also individual B cells from patients with SLE for the expression of RAG mRNA. RESULTS: Analysis of bulk mRNA indicated that RAG1 and RAG2 mRNA were found routinely in peripheral B cells of patients with active SLE, but not in healthy subjects. When assessed on a single-cell basis, there was a 3-fold increase in the frequency of RAG1- and RAG2-expressing B cells in SLE patients compared with healthy subjects. Notably, B cells expressing both RAG1 and RAG2 mRNA expressed only IgD mRNA, but not IgG mRNA. Fifty percent of RAG-expressing B cells also expressed VpreB mRNA, whereas all expressed CD154 mRNA. Phenotypic analysis indicated that RAG-expressing B cells were activated, mature B cells. CONCLUSION: These results indicate that RAG expression is up-regulated in peripheral IgD+ and VpreB+ B cells of patients with active SLE. These cells may contribute to the immunoregulatory abnormalities in patients with SLE.     

Glucocorticoid therapy suppresses Wnt signaling by reducing the ratio of serum Wnt3a to Wnt inhibitors,sFRP-1 and Wif-1

Clinical Rheumatology - Our previous study suggested that suppression of Wnt/β-catenin signaling by increasing serum Wnt co-receptor inhibitors, sclerostin and Dickkopf-1, impairs bone...     

Clinical characteristics of COVID-19 patients with underlying rheumatic diseases in Japan: data from a multicenter observational study using the COVID-19 Global Rheumatology Alliance physician-reported registry

Clinical Rheumatology - To describe clinical characteristics of patients in Japan with coronavirus disease 19 (COVID-19) and pre-existing rheumatic disease and examine the possible risk factors...     

Safety,pharmacokinetics, and efficacy of E6011, an antifractalkine monoclonal antibody,in a first-in-patient phase 1/2 study on rheumatoid arthritis

Objective: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558).

Methods: Active RA patients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks.

Results: Twelve, 15, and 10 subjects were enrolled in the 100, 200, and 400?mg cohorts, respectively. No severe adverse events (AEs) or deaths occurred, and no major differences were observed in the incidence or severity of AEs across the cohorts. Serum E6011 concentrations increased dose dependently. American College of Rheumatology (ACR) 20, 50, and 70 responses at week 12 were 75.0%, 33.3%, and 8.3% in the 100?mg cohort; 66.7%, 20.0%, and 13.3% in the 200?mg cohort; and 60.0%, 30.0%, and 20.0% in the 400?mg cohort, respectively.

Conclusions: E6011 appeared to be safe and well tolerated in RA patients during this 12-week treatment period, suggesting that E6011 has an effective clinical response in active RA patients.     

The effect of synthetic retinoid, Am80, on T helper cell development and antibody production in murine collagen-induced arthritis

Retinoids are known to promote T helper (Th)2 and regulatory T cell (Treg) differentiation, and suppress Th1 and Th17 in vitro. Am80, a synthetic retinoid, is reported to ameliorate collagen-induced arthritis (CIA). The aims of this study are to determine the effects of Am80 on CIA in detail, and on Th development and antibody (Ab) production in vivo. Murine CIA was induced by immunization with bovine type II collagen (CII) at days 1 and 22. Treatment with Am80 from day 1 to 35 significantly lowered clinical arthritis score, suppressed cellular infiltration and bone destruction in the joint, decreased interleukin (IL)-17 and increased interferon (IFN)-γ production by CII-stimulated splenocytes, and decreased proportion of Foxp3⁺ splenic CD4 T cells and serum anti-CII Ab levels. Thus, Am80 inhibited Th17 and Treg and enhanced Th1 differentiation in vivo. In contrast, Am80 applied from day 15 to 35 did not alter arthritis score, IL-17 or IFN-γ production by CII-stimulated splenocytes, but decreased the proportion of Foxp3⁺ splenic CD4 T cells and serum anti-CII Ab levels. Am80 exhibits inhibitory effects on CIA and might regulate both Th development and Ab production in vivo. Decreased Th17 by treatment with Am80 might be responsible for the attenuation of arthritis.     

Pneumatosis cystoides intestinalis following lupus enteritis and peritonitis

We describe a case of systemic lupus erythematosus (SLE) with enteritis and peritonitis who later developed pneumatosis cystoides intestinalis (PCI). A 35-year-old woman with SLE relapsed with enteritis and peritonitis. Prednisolone (PSL) effectively improved her symptoms. However, 6 weeks later, she developed PCI. Tapering of PSL, administration of intravenous cyclophosphamide, prokinetic agents and antibiotics, bowel rest with intravenous hypernutrition therapy and hyperbaric oxygen therapy successfully improved PCI. Although PCI is a rare complication of SLE, the present case suggests that lupus enteritis could be a risk factor for PCI, and that high-dose PSL could cause additional insult to PCI.