11 research outputs found
Viscosity of Freeze-Concentrated Solution Confined in Micro/Nanospace Surrounded by Ice
An aqueous solution
separates into ice and a freeze-concentrated
solution (FCS) when frozen at temperatures above the eutectic point.
The FCS acts as important reaction media in natural environment and
industrial processes. The viscosities of the FCS in frozen glycerol/water
solutions are evaluated by two spectrometric methods with different
principles: (1) the reaction rate of the diffusion-controlled emission
quenching and (2) fluorescence correlation spectroscopy. Thermodynamics
indicates that the concentration of glycerol in the FCS is constant
at a constant temperature regardless of the glycerol concentration
in the original solution before freezing (<i>c</i><sub>gly</sub><sup>ini</sup>). However,
the viscosity of the FCS measured at a given temperature increases
with decreasing <i>c</i><sub>gly</sub><sup>ini</sup>, and this trend becomes more pronounced
with decreasing measurement temperature. Further, the viscosity of
the FCS in a rapidly frozen solution is higher than that in a slowly
frozen solution. These results suggest that the viscosity of the FCS
depends on the size of the space in which the FCS is confined and
is enhanced in smaller spaces. This result agrees well with several
reports of anomalous phenomena in a microspace confined in ice. These
phenomena should originate from the fluctuation of the ice/FCS interface,
which is macroscopically stable but microscopically dynamic and undergoes
continuous freezing and thawing. Thus, the FCS near the interface
has ice-like physicochemical properties and structures, giving higher
viscosity than the corresponding bulk solution
OX40 ligand expressed in glioblastoma modulates adaptive immunity depending on the microenvironment: a clue for successful immunotherapy
Background: Glioblastoma is the most malignant human brain tumor and has a dismal prognosis; however, some patients show long-term survival. The interaction between the costimulatory molecule OX40 and its ligand OX40L generates key signals for T-cell activation. The augmentation of this interaction enhances antitumor immunity. In this present study, we explored whether OX40 signaling is responsible for antitumor adaptive immunity against glioblastoma and also established therapeutic antiglioma vaccination therapy. Methods: Tumor specimens were obtained from patients with primary glioblastoma (n = 110) and grade III glioma (n = 34). Quantitative polymerase chain reaction (PCR), flow cytometry, and immunohistochemistry were used to analyze OX40L expression in human glioblastoma specimens. Functional consequences of OX40 signaling were studied using glioblastoma cell lines, mouse models of glioma, and T cells isolated from human subjects and mice. Cytokine production assay with mouse regulatory T cells was conducted under hypoxic conditions (1.5% O_2). Results: OX40L mRNA was expressed in glioblastoma specimens and higher levels were associated with prolonged progression-free survival of patients with glioblastoma, who had undergone gross total resection. In this regard, OX40L protein was expressed in A172 human glioblastoma cells and its expression was induced under hypoxia, which mimics the microenvironment of glioblastoma. Notably, human CD4 T cells were activated when cocultured in anti-CD3-coated plates with A172 cells expressing OX40L, as judged by the increased production of interferon-γ. To confirm the survival advantage of OX40L expression, we then used mouse glioma models. Mice bearing glioma cells forced to express OX40L did not die during the observed period after intracranial transplantation, whereas all mice bearing glioma cells lacking OX40L died. Such a survival benefit of OX40L was not detected in nude mice with an impaired immune system. Moreover, compared with systemic intraperitoneal injection, the subcutaneous injection of the OX40 agonist antibody together with glioma cell lysates elicited stronger antitumor immunity and prolonged the survival of mice bearing glioma or glioma-initiating cell-like cells. Finally, OX40 triggering activated regulatory T cells cultured under hypoxia led to the induction of the immunosuppressive cytokine IL10. Conclusion: Glioblastoma directs immunostimulation or immunosuppression through OX40 signaling, depending on its microenvironment