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IntroductionSince treatment modalities for metastatic recurrent triple-negative breast cancer (mrTNBC) are limited, a novel treatment approach including immunotherapy is required. We have developed a novel regimen of personalized peptide vaccination (PPV), in which vaccine antigens are individually selected from a pool of different peptide candidates based on the pre-existing host immunity. Herein we conducted a phase II study of PPV for metastatic recurrent breast cancer patients to investigate the feasibility of PPV for mrTNBC.MethodsSeventy-nine patients with metastatic recurrent breast cancer who had metastases and had failed standard chemotherapy and/or hormonal therapy were enrolled. They were subgrouped as the mrTNBC group (n = 18), the luminal/human epidermal growth factor receptor 2 (HER2)-negative group (n = 41) and the HER2-positive group (n = 18), while the remaining two patients had not been investigated. A maximum of four human leukocyte antigen (HLA)-matched peptides showing higher peptide-specific immunoglobulin G (IgG) responses in pre-vaccination plasma were selected from 31 pooled peptide candidates applicable for the four HLA-IA phenotypes (HLA-A2, -A24, or -A26 types, or HLA-A3 supertypes), and were subcutaneously administered weekly for 6 weeks and bi-weekly thereafter. Measurement of peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses along with other laboratory analyses were conducted before and after vaccination.ResultsNo severe adverse events associated with PPV were observed in any of the enrolled patients. Boosting of CTL and/or IgG responses was observed in most of the patients after vaccination, irrespective of the breast cancer subtypes. There were three complete response cases (1 mrTNBC and 2 luminal/HER2-negative types) and six partial response cases (1 mrTNBC and 5 luminal/HER2-negative types). The median progression-free survival time and median overall survival time of mrTNBC patients were 7.5 and 11.1 months, while those of luminal/HER2-negative patients were 12.2 and 26.5 months, and those of HER2-positive patients were 4.5 and 14.9 months, respectively.ConclusionsPPV could be feasible for mrTNBC patients because of the safety, immune responses, and possible clinical benefits.Clinical Trial Registration NumberUMIN000001844 (Registration Date: April 5, 2009)

Duration of breastfeeding, season of birth, pet ownership, household income, and the number of siblings were associated with the prevalence of childhood eczema in a nationwide web survey.

A population-based Web survey showed an association between several factors and the control of paediatric asthma. The assessment of these factors may help identify the children at risk with uncontrolled asthma.

Tumor necrosis factor-alpha (TNF-a)-inducing activity of several mycoplasmas including Mycoplasma pneumoniae, a causative agent in human respiratory infectious diseases, was investigated. Purified peritoneal macrophages from BALB/c mice markedly enhanced their cytotoxic activity to Meth A cells, when cultured with either viable or non-viable mycoplasmas. The supernatants of the macrophage culture with mycoplasmas, M. pneumoniae and Acholeplasma laidlawii, showed the potent cytotoxic activity to TNF-a-sensitive L cells but not to TNF-a-insensitive L cells. Addition of anti-TNF-a antiserum inhibited completely the cytotoxic activity of these supernatants, indicating that a major part of the cytotoxic activity might be due to TNF-a. Various other mycoplasmas, either glucose-or arginineutilizing species, as far as tested showed also the potent activity to produce TNF-a. These results strongly suggest the possibility that mycoplasmas possess the activity of TNF-a induction which might be responsible for a part of enhancement of cytotoxic activity of macrophages and resistance to infection with mycoplasmas in vivo.Mycoplasmas have been isolated from almost all domestic and laboratory animals and man, and often cause the mycoplasma diseases such as respiratory infections and others. In humans, Mycoplasma pneumoniae is the causative agent of upper respiratory tract infections and pneumonia (14). These microorganisms lack the specific cell wall components of bacteria, such as diaminopimelic and muramic acids, and exist predominantly in an extracellular environment in close association with the cell plasma membrane (5). Although mycoplasmas can cause minimal morphological changes in mycoplasma-infected cell cultures, the possible simultaneous effects are numerous, in mycoplasma-infected immunocytes, such as lymphocytes, macrophages, and hybridoma cell lines, including enhancement of productions of immunoglobulin (26), cytokines (23), and interferon (4, 10, 24). Furthermore, the cytotoxicity of macrophages (17,20) and natural killer (NK) cells (7,18) to target cells are enhanced, when these cell lines were contaminated with mycoplasmas. Although the mechanisms of enhancement of macrophages-mediated 231