The recurrence rates of Hepatocellular carcinoma (HCC) are high, necessitating novel and effective adjuvant therapies. Therefore, we conducted a phase II study of glypican-3 (GPC3) peptide vaccine as an adjuvant therapy for HCC patients. Forty-one patients with initial HCC who had undergone surgery or radiofrequency ablation (RFA) were analyzed in this phase II, open-label, single-arm trial. Ten vaccinations were performed for 1 y after curative treatment. We also investigated case-control subjects, where selected patients treated surgically during the same period were analyzed. The expression of GPC3 in the available primary tumors was determined by immunohistochemical analysis. Six patients received RFA therapy while 35 received surgery. The recurrence rate tended to be lower in the 35 patients treated with surgery plus vaccination compared to 33 patients who underwent surgery alone (28.6% vs. 54.3% and 39.4% vs. 54.5% at 1 and 2 y, respectively; p = 0.346, 0.983). Twenty-five patients treated with surgery and vaccination had GPC3-positive tumors; the recurrence rate in this group was significantly lower compared to that in 21 GPC3-positive patients who received surgery only (24% vs. 48% and 52.4% vs. 61.9% at 1 and 2 y, respectively; p = 0.047, 0.387). The GPC3 peptide vaccine improved the 1-y recurrence rate in patients with GPC3-positive tumors. This study demonstrated that GPC3 expression by the primary tumor may be used as a biomarker in a putative larger randomized clinical trial to determine the efficacy of the GPC3-derived peptide vaccine.

Increases in blood volume are observed during normal gestation and these are reversed shortly after delivery. Although both atrial (A-type) natriuretic peptide (ANP) and brain (B-type) natriuretic peptide (BNP) have been described, the role of these peptides in pregnancy and the postpartum period are unclear. This study was designed to examine the effects of pregnancy, labour and delivery on plasma levels of ANP and BNP. Plasma levels of ANP and BNP were determined during normal pregnancy, 30 min after separation of the placenta (immediately postpartum) and between 5 and 72 h postpartum (late postpartum; puerperium). Since the assay sensitivity was 20 pg/ml plasma (for both ANP and BNP), values less than this were assigned a value of 20 pg/ml to calculate means. Plasma levels of ANP and BNP were significantly higher at term pregnancy than during the first trimester (ANP increased from 20 +/- 0.2 to 57 +/- 10 pg/ml (S.E.M.), P < 0.001; BNP increased from 25 +/- 2 to 49 +/- 9 pg/ml, P < 0.01). The plasma level of ANP then rose to 157 +/- 38 pg/ml 30 min after separation of the placenta, being significantly (P < 0.01) higher than that seen at term pregnancy. It declined significantly (P < 0.001) to 32 +/- 3 pg/ml in the late postpartum period. In contrast, the plasma level of BNP 30 min after separation of the placenta was 80 +/- 25 pg/ml, and increased to 116 +/- 17 pg/ml in the late postpartum period, significantly (P < 0.01) higher than the level at term pregnancy.(ABSTRACT TRUNCATED AT 250 WORDS)

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Lung cancer is the leading cause of cancer-related deaths worldwide. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib and erlotinib, have demonstrated marked clinical activity against non-small cell lung cancer (NSCLC) harboring activating epidermal growth factor receptor (EGFR) mutations. However, in most cases, patients develop acquired resistance to EGFR-TKI therapy. The threonine to methionine change at codon 790 of EGFR (EGFR T790M) mutation is the most common acquired resistance mutation, and is present in ~50% cases of TKI resistance. New treatment strategies for NSCLC patients harboring the EGFR T790M mutation are required. We evaluated the immunogenicity of an antigen derived from EGFR with the T790M mutation. Using BIMAS we selected several EGFR T790M-derived peptides bound to human leukocyte antigen (HLA)-A*02:01. T790M-A peptide (789–797) (IMQLMPFGC)-specific cytotoxic T lymphocytes (CTLs) were induced from peripheral blood mononuclear cells (PBMCs) of HLA-A2+ healthy donors. An established T790M-A-specific CTL line showed reactivity against the NCSLC cell line, H1975-A2 (HLA-A2+, T790M+), but not H1975 (HLA-A2−, T790M+), and the corresponding wild-type peptide (ITQLMPFGC)-pulsed T2 cells using an interferon-γ (IFN-γ) enzyme-linked immuno spot (ELISPOT) assay. This CTL line also demonstrated peptide-specific cytotoxicity against H1975-A2 cells. This finding suggests that the EGFR T790M mutation-derived antigen could be a new target for cancer immunotherapy.

Muscovy ducks (Cairina moschata) showed abnormal feathering, leg weakness, and high mortality. A virus was isolated from these ducks after several blind passages in embryonating Muscovy duck eggs. The isolate was resistant to chloroform, to pH 3.2, and to 65 C for 30 min. Electron microscopy showed that the isolate was an icosahedral and nonenveloped virus 20-22 nm in diameter. The isolate reacted with an antiserum against a goose parvovirus in agar gel precipitation tests. After 15 passages of the isolate in embryonating eggs, the isolate was adapted to Muscovy duck embryo fibroblasts. The adapted virus developed cytopathic effects and made clear plaques on sheets of the fibroblasts. When 5-iodo-2-deoxyuridine was added to the culture medium, virus growth was inhibited. From the data shown above, the isolate was identified as a goose parvovirus.