Nivolumab Versus Gemcitabine or Pegylated Liposomal Doxorubicin for Patients With Platinum-Resistant Ovarian Cancer: Open-Label, Randomized Trial in Japan (NINJA)

PURPOSE: This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS: Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS: Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION: Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer

Detection of Antilymphocyte Antibody with Two-Color Method in Systemic Lupus Erythematosus and Its Heterogeneous Specificities against Human T-Cell Subsets

The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tγ) and lacking (Tγ[-]) cells, 64% of ALA showed preferential reactivity with Tγ cells and 14% with Tγ(-) cells. The remainder had no selective reactivity against Tγ or Tγ(-) cells. Tγ cells were shown to have suppressor activity, whereas Tγ(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tγ cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tγ(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets

Dating Hydrothermal Minerals in Active Hydrothermal Fields in the Southern Mariana Trough

Ages of hydrothermal mineral samples were determined by 230Th/234U radioactive disequilibrium dating technique. Sulfidesamples were collected from four active sites in the mostsouthern region of the Mariana Trough; Snail site (located onthe spreading axis), Archaean site (located on a mound 1.5 kmdistant from the axis), Pika site (located on an off-axis knoll4.9 km distant from the axis) and Urashima site (located on thenorthern slope of the same knoll). Samples were collected fromactive hydrothermal vents and inactive sulfide spires duringdive expeditions of YK10-10 cruise using the submersibleSHINKAI6500. In addition, massive sulfide ores were coredby shallow drilling using a BMS (Benthic Multi-coringSystem) during the TAIGA10 cruise.Sulfide ores collected from the hydrothermal mound of theArchaean site range in age from < 100 to 3520 years old. Thegrowth rate of the massive sulfide ore body is calculated to be0.12 - 1.5 mm/year based on results of the core samples. Theseresults suggest that a few thousand years of continuoushydrothermal activity would be required for formation ofmassive ore deposit that overlays the hydrothermal mound 50-100 m high and 250-300 m in diameter.Sulfide ores collected from the two hydrothermal fieldslocated on the off-axis knoll (Pika and Urashima sites) are upto 9000 years old. When combined with geophysical evidencefor crustal velocity anomaly, this mineralization is consideredto be in the late-stage of the hydrothermal activity, and relatedto a cooling magma body.Goldschmidt　201