Effect of heat therapy using magnetic nanoparticles conjugated with cationic liposomes on prostate tumor in bone

BACKGROUND: We have developed magnetite nanoparticles conjugated with cationic liposomes (MCLs) to induce intracellular hyperthermia with exposure to an alternating magnetic field (AMF). We have previously demonstrated the hyperthermic effect of MCLs against certain types of malignant tumor cells in vivo. Here, we examine the effects of MCL + AMF heat therapy on prostate cancer tissue in a bone microenvironment and on bone destruction in a rat model. MATERIALS AND METHODS: Rat prostate cancer nodules were transplanted onto the calvaria of 6-week-old F344 male rats. MCLs were injected into the tumor which reached 7 mm in diameter, and then the animals were exposed to repeated AMF irradiation. The distribution of MCL, tumor necrosis, cell proliferation, and bone destruction in the bone microenvironment were evaluated. RESULTS: MCL + AMF heat therapy suppressed tumor growth on the calvaria, and histologically, the induction of a necrotic mass was observed around magnetic particles in the tumor. The bone destruction index, which indicates the degree of osteolysis associated with prostate tumor growth in the bone microenvironment, was 34.8% in the MCL group and 67.2% in the control group with significant difference. However, almost half of rats were dead in this experiment. CONCLUSION: MCL + AMF heat therapy suppressed tumor proliferation in the bone microenvironment, in addition to bone destruction. However, this method may exhibit side effects for central nerve system. If MCL are specifically taken into the prostate cancer cells in the bone microenvironment, this method may be useful for the treatment of bone metastatic lesions of prostate cancer.     

GSK2656157, a PERK inhibitor,reduced LPS-induced IL-1β production through inhibiting Caspase 1 activation in macrophage-like J774.1 cells

IL-1β is one of the inflammatory cytokines and is cleaved from pro-IL-1β proteolytically by activated Caspase 1. For the activation of Caspase 1, inflammasome was formed by two signals, what is called, priming and triggering signals. In this study, it was found that mouse macrophage J774.1 cells, when treated by single large amount of lipopolysaccharide (LPS), produced a significant amount of IL-1β. On the other hand, IL-1β production was not detected when treated by a single, small amount of LPS. Then, focusing on endoplasmic reticulum (ER) stress response among stress responses induced by a large amount of LPS, when GSK2656157, a PERK inhibitor, was used for inhibition of ER stress, GSK2656157 reduced IL-1β production dose-dependently. Next, when Thapsigargin, an ER stress reagent, was added with LPS, IL-1β production increased more than by LPS alone. Thus, these results suggested that ER stress was involved in LPS-induced IL-1β production. When the activation of Caspase 1 was examined by fluorescence activated cell sorter analysis, it was found that GSK2656157 inhibited LPS-induced Caspase 1 activation. Further, it was confirmed that GSK2656157 did not affect LPS-induced TNF-α production and activation of NF-κB and specifically inhibited the PERK/eIF-2α pathway. Therefore, it was found that GSK2656157 specifically inhibited ER stress induced by large amount of LPS and reduced LPS-induced IL-1β production through inhibition of Caspase 1 activation.     

Immunological Identification of Blood Group Pk Antigen on Normal Human Erythrocytes and Isolation of Anti-Pk with Different Affinity

The P1 and Pk blood group glycolipid antigens have the common terminal disaccharide, Gal(alpha, 1-4)Gal, but previous studies indicated that anti-P1 from P2 individuals does not cross-react with Pk antigen. In this paper, the specificities of anti-P1 and anti-Pk were analyzed carefully by complement fixation and hemagglutination techniques and the following results were obtained: (1) Anti-P1 from P2 serum was not absorbed with the Pk glycolipid (CTH), but this antigen absorbed all anti-P1 and anti-Pk (anti-P1Pk) antibodies from the sera of four p individuals. Most of the anti-P1Pk antibodies were IgG, but the anti-p1 from the P2 individual was IgM. (2) The Pk antigen on normal P2 erythrocytes was not 'cryptic'. It was reactive with p serum from which the anti-P antibodies were removed by absorption with the P glycolipid (globoside). This was not appreciated previously because, in order to make anti-Pk reagents, p sera (anti-P1PPk) were absorbed with P1 cells which contain CTH. (3) The anti-P1Pk antibodies in p sera were separated by partial absorption with P1 erythrocytes and elution from the absorbing cells, into two fractions that differ markedly in their affinity for alpha-methyl-D-galactoside and the oligosaccharides prepared from CTH.