PLoS One. 2009; 4(8): e6520Yang HZ, Cui B, Liu HZ, Mi S, Yan J, Yan HM, Hua F, Lin H, Cai WF, Xie WJ, Lv XX, Wang XX, Xin BM, Zhan QM, Hu ZWBACKGROUND: Metastasis is the most pivotal cause of mortality in cancer patients. Immune tolerance plays a crucial role in tumor progression and metastasis. METHODS AND FINDINGS: In this study, we investigated the potential roles and mechanisms of TLR2 signaling on tumor metastasis in a mouse model of intravenously injected B16 melanoma cells. Multiple subtypes of TLRs were expressed on B16 cells and several human cancer cell lines; TLR2 mediated the invasive activity of these cells. High metastatic B16 cells released more heat shock protein 60 than poor metastatic B16-F1 cells. Importantly, heat shock protein 60 released by tumor cells caused a persistent activation of TLR2 and was critical in the constitutive activation of transcription factor Stat3, leading to the release of immunosuppressive cytokines and chemokines. Moreover, targeting TLR2 markedly reduced pulmonary metastases and increased the survival of B16-bearing mice by reversing B16 cells induced immunosuppressive microenvironment and restoring tumor-killing cells such as CD8(+) T cells and M1 macrophages. Combining an anti-TLR2 antibody and a cytotoxic agent, gemcitabine, provided a further improvement in the survival of tumor-bearing mice. CONCLUSIONS AND SIGNIFICANCE: Our results demonstrate that TLR2 is an attractive target against metastasis and that targeting immunosuppressive microenvironment using anti-TLR2 antibody is a novel therapeutic strategy for combating a life-threatening metastasis.
Homeopathy. 2009 Jul; 98(3): 165-8Waisse-Priven S, Jurj G, Lima Thomaz LC, Tierno SA, Filho WL, Sos ABThis paper describes the successful outcome of homeopathic treatment in a case of resistant livedoid vasculopathy (LV). LV is a rare disease characterized by chronic recurrent and painful ulceration of the lower limbs, frequently associated to atrophie blanche (AB), probably due to procoagulant conditions. Most literature reports single or very few cases; response to treatment is difficult, even resistant. This patient suffered LV for 7 years before seeking homeopathic treatment; ulcers recurred frequently, at intervals less than 3 months, in spite of continual use of pentoxyfilline. Configuration of signs and symptoms strongly pointed out to the prescription of homeopathic remedy Sepia succus that promptly elicited significant improvement of LV and the patient's overall state (non suppressive treatment). Considerations are made on the value of single case reports and the reliability of prescriptions grounded on consistent signs and coherence among the manifold features of individual disease.
Rapid Commun Mass Spectrom. 2009 Jul 28; 23(17): 2724-2732Wang Y, Ding C, Du K, Xiao Y, Wu C, Zhang J, Qin H, Du GXiao-xu-ming decoction (XXMD) prescription is a traditional Chinese prescription that has been widely used to treat theoplegia and the sequela of theoplegia. Modern pharmacological research has also indicated that the active fraction from XXMD is able to treat cardiovascular diseases and Alzheimer's disease. In the study reported here, high-performance liquid chromatography coupled with Fourier transform ion cyclotron resonance mass spectrometry (HPLC/FTICR-MS) was developed to identify active compounds and their metabolites after oral administration of active fraction from Xiao-xu-ming decoction to rats, using parent mass list triggered data-dependent multiple-stage mass analysis at a resolving power of 100 000 in the external calibration mode. The mass accuracies obtained for full-scan MS were within 2 ppm in most cases. Fifteen constituents were identified in the active fraction from XXMD and the biological samples of rats. The fragmentation behaviors of these constituents were summarized which would be helpful for structural characterization. The profiles of the constituents in the active fraction and biological samples of rats were obtained which provided us with much information for a better understanding of the chemical basis of the pharmacologic actions of XXMD. Copyright (c) 2009 John Wiley & Sons, Ltd.
Homeopathy. 2009 Jul; 98(3): 160-4de Araújo FR, de Castro CM, Severo MS, Diniz Mde F, Viana MT, Evêncio LBOBJECTIVE: The purpose of this study was to assess the bacteriological response in alveolitis in rats treated with the homeopathic medicine Merc solubilis (Merc sol.) 12 cH. METHODS: The study was randomized and observer blind. The animals were anesthetized and the upper right incisor extracted resulting in alveolitis. Animals were randomly assigned to groups (n=18/group): Water control, Alcohol control and Merc sol. 12 cH. These groups were subsequently divided into 3 subgroups (n=6/subgroup): Early Euthanasia (EE), Mid Euthanasia (ME) and Late Euthanasia (LE), killed at the 6th, 15th and 21st days respectively. The perialveolar microbiota was collected by swab in Brain Heart Infusion (BHI) for seeding and bacterioscopy. After seeding, the Petri dishes were incubated at 37 degrees C for 48 h. RESULTS: Quantitative and qualitative changes were observed in the perialveolar microbiota when the groups were compared. Water control and Alcohol control had the highest counts of pathogenic bacteria, the microbiotica of the Merc sol. group remained closer to normal. CONCLUSIONS: Merc sol. 12 cH did not reduce bacterial growth, but the microbiotica remained within the parameters of normality, obtaining the best results at 21 days after treatment.