Spontaneous and cyclophosphamide-enhanced metastasis inhibited by traditional Chinese medicine (TCM) herbal mixture LQ.

e22209 Background: Cyclophosphamide pretreatment of mice enhances metastatsis of HT1080 human fibrosarsoma cells (Cancer Res. 68, 516-520, 2008). Methods: HT1080 human fibrosarsoma cells were injected into the footpad or were injected into the epigastric cranialis vein of mice pre-treated with cyclophosphamide (CYC) or a combination of CYC and the herbal mixture LQ. The efficacy was monitored through dynamic subcellular imaging of trafficking of cancer cells in lymph nodes and blood vessels in live mice. Results: LQ significantly inhibited HT1080 spontaneous metastases to local lymph nodes in the foot-pad-injection model. In the control group, 100% of mice had lymph node metastasis, compared to 12.5% of the mice in the LQ treatment group. LQ also significantly inhibited CYC-enhanced experimental metastasis in the epigastric cranialis vein injection model. LQ prolonged the overall survival of mice in the spontaneous-lymph-node metastatic footpad-injection model. Conclusions: The TCM herbal mixture LQ shows promis to inhibit metastasis and will be further tested in other metastatic models.

Expression of TLR4-MyD88 and NF-κB in the Iris during Endotoxin-Induced Uveitis

Purpose. To observe the expression of Toll-like receptor-4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor kappa B p65 (NF-κB p65) in iris tissue during endotoxin-induced uveitis (EIU) and evaluate the significance of these factors in uveitis.Methods. Wistar rats were randomly divided into 5 groups (0 h, 12 h, 24 h, 48 h, and 72 h, n = 10/group). Animal model of acute anterior uveitis was established by a hind footpad injection of 200 μgCholera vibrio LPS. Expression of TLR4, MyD88, and NF-κB p65 in iris ciliary body tissue was detected through immunohistochemical staining.Results. Expression of TLR4 was not detected in normal iris-ciliary body complex, TLR4 positive cells with round morphology appeared in the iris stroma 12 hours after injection, significantly increased(P<.001)48 hours after injection, and decreased gradually 72 hours after injection. Expression of MyD88 and NF-κB p65 is consistent with the change of the TLR4.Conclusions. The increased expression of TLR4 and its downstream signal transduction moleculesMyD88, NF-κB p65 indicate the potential role of pathway in the pathogenesis of acute anterior uveitis (AAU).

Positive responses to imipramine in the popliteal lymph node assay are due to primary irritation

The popliteal lymph node (PLN) assay has long been proposed as a tool to detect immunotoxicants with the potential to induce systemic autoimmunity. A major problem hampering the further validation of this assay is the need to rule out irritants that cause false-positive PLN responses. The anti-depressant, imipramine, has not been reported to induce systemic autoimmune reactions in treated patients, but has been repeatedly found positive in the PLN assay, suggesting that this is a false-positive response. To test this hypothesis, the effects of imipramine were compared to those of 50% ethanol in C57Bl/6 mice. Footpad edema was evidenced in the few days after injection of both ethanol and imipramine. T-cell depletion using monoclonal antibodies against either CD4+ or CD8+T-lymphocytes prior to the PLN assay did not influence the responses to either ethanol or imipramine. Cytokine (TNF, IL-1, IL-1, IL-2R, IL-6, IL-12 and IFN-) fingerprinting of the PLNs after injection of ethanol and imipramine evidenced the same pattern of responses. These results indicate a closely similar pattern of responses following the footpad injection of either imipramine or ethanol. The conclusion can be drawn that imipramine induces positive responses in the PLN assay via primary (nonspecific) irritation.