BackgroundThe treatment of intratumoral dentritic cells (DCs) commonly fails because it cannot evoke immunity in a poor tumor microenvironment (TME). Modulated electro-hyperthermia (mEHT, trade-name: oncothermia) represents a significant technological advancement in the hyperthermia field, allowing the autofocusing of electromagnetic power on a cell membrane to generate massive apoptosis. This approach turns local immunogenic cancer cell death (apoptosis) into a systemic anti-tumor immune response and may be implemented by treatment with intratumoral DCs.MethodsThe CT26 murine colorectal cancer model was used in this investigation. The inhibition of growth of the tumor and the systemic anti-tumor immune response were measured. The tumor was heated to a core temperature of 42 °C for 30 min. The matured synergetic DCs were intratumorally injected 24 h following mEHT was applied.ResultsmEHT induced significant apoptosis and enhanced the release of heat shock protein70 (Hsp70) in CT26 tumors. Treatment with mEHT-DCs significantly inhibited CT26 tumor growth, relative to DCs alone or mEHT alone. The secondary tumor protection effect upon rechallenging was observed in mice that were treated with mEHT-DCs. Immunohistochemical staining of CD45 and F4/80 revealed that mEHT-DC treatment increased the number of leukocytes and macrophages. Most interestingly, mEHT also induced infiltrations of eosinophil, which has recently been reported to be an orchestrator of a specific T cell response. Cytotoxic T cell assay and ELISpot assay revealed a tumor-specific T cell activity.ConclusionsThis study demonstrated that mEHT induces tumor cell apoptosis and enhances the release of Hsp70 from heated tumor cells, unlike conventional hyperthermia. mEHT can create a favorable tumor microenvironment for an immunological chain reaction that improves the success rate of intratumoral DC immunotherapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1690-2) contains supplementary material, which is available to authorized users.

Diabetes augments periodontal destruction by reducing the proliferating capability and activating resorptive activities. Presence of the AGE-RAGE axis without diabetes implies that it is involved in the regulation of inflammation.

The superoxide scavenging effects of fifteen coumarins were tested on the xanthine-xanthine oxidase-cytochrome C system. The results showed that fraxetin(10) displayed the strongest activity, and its percent inhibition at 100, 10 and 1 muM were 100, 100 and 53.13% respectively. Esculetin(4) showed the second strongest activity resulting in percent inhibition at 100 and 10 muM were 87.16 and 52.38% respectively. Both fraxetin(10) and esculetin(4) have been isolated from the plant, Fraxinus bungeana DC (Oleaceae) which has been used in folk medicine as an analgesic and anti-inflammatory medicine. It seems that two phenolic hydroxy groups in the ortho position in the molecule of coumarins play an important role in scavenging activity.

Diploptene(1), beta-sitosterol(2), a mixture of 6'-O-(E-P-coumaroyl)-alpha-glucopyranose and 6'-O-(E-P-coumaroyl)-beta-glucopyranose(3), a mixture of 6'-O-(E-P-caffeoyl)-alpha-glucopyranose and 6'-O-(E-P-caffeoyl)-beta-glucopyranose(4), caffeic acid(5) and astragalin(6) were isolated from an ethanolic extract of the leaves of Alsophila spinulosa Hook Tryon (Cyatheaceae). The plant has been used in folk medicine for hepatitis, gout, rheumatism, and tumor and these compounds were tested for their inhibitory effect on xanthine oxidase. Caffeic acid was the most potent constituent (IC50 = 39.21 microM; Ki = 28.2 microM) and was an uncompetitive inhibitor of the enzyme with respect to the substrate xanthine.