A multi-targeted approach to suppress tumor-promoting inflammation

Cancers harbor significant genetic heterogeneity and patterns of relapse following many therapies are due to evolved resistance to treatment. While efforts have been made to combine targeted therapies, significant levels of toxicity have stymied efforts to effectively treat cancer with multi-drug combinations using currently approved therapeutics. We discuss the relationship between tumor-promoting inflammation and cancer as part of a larger effort to develop a broad-spectrum therapeutic approach aimed at a wide range of targets to address this heterogeneity. Specifically, macrophage migration inhibitory factor, cyclooxygenase-2, transcription factor nuclear factor-κB, tumor necrosis factor alpha, inducible nitric oxide synthase, protein kinase B, and CXC chemokines are reviewed as important antiinflammatory targets while curcumin, resveratrol, epigallocatechin gallate, genistein, lycopene, and anthocyanins are reviewed as low-cost, low toxicity means by which these targets might all be reached simultaneously. Future translational work will need to assess the resulting synergies of rationally designed antiinflammatory mixtures (employing low-toxicity constituents), and then combine this with similar approaches targeting the most important pathways across the range of cancer hallmark phenotypes

Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

<p>Abstract</p> <p>Background</p> <p>Several <it>Echinacea </it>species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of <it>E. purpurea </it>([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.</p> <p>Results</p> <p>Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (<it>Cdh10</it>, <it>Itga6</it>, <it>Cdh1</it>, <it>Gja1 </it>and <it>Mmp8</it>), or were chemokines (<it>Cxcl2, Cxcl7) </it>or signaling molecules (<it>Nrxn1, Pkce </it>and <it>Acss1</it>). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. <it>In vitro </it>flow cytometry analysis of chemotaxis-related receptors and <it>in vivo </it>cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.</p> <p>Conclusion</p> <p>Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of <it>Echinacea </it>or other candidate medicinal plants.</p

Enhanced Anti-tumor Effect of Modified Vaccinia Virus Expressing Human-gp100 Antigen and Rantes in Cancer Vaccine Approach

[[sponsorship]]農業生物科技研究中心[[note]]已出版;沒有審查制度;具代表

Protective Immune responses against Porcine Circovirus Type 2 Infection Generated by a Recombinant Modified Vaccinia Virus Expressing the Viral ORF antigens as Vaccines

[[sponsorship]]農業生物科技研究中心[[note]]已出版;沒有審查制度;具代表

Antiinflammatorisch wirksame Phytotherapeutika und ihr mögliches Potential bei tumorkranken Menschen

Die Wirkstoffe pflanzlicher Arznei- und Heilmittel sind pleiotrope Vielstoffgemische mit Multi-Target Eigenschaften einschlieβlich antiinflammatorischer Wirkungen. Eine pleiotrope Entzündungshemmung könnte bei tumorkranken Menschen als Versuch der Verhinderung bzw. Verzögerung der Metastasierung eine bedeutsame Rolle spielen. Zahlreiche experimentelle Daten für europäische wie auch auβereuropäische Pflanzen und verschiedene phytotherapeutische Kombinationen weisen auf eine solche Möglichkeit hin. Trotz der bislang nur geringen Anzahl klinischer Untersuchungen könnten derartige phytotherapeutische Behandlungsversuche vertretbar erscheinen, wenn für solche Arznei- und Heilpflanzen aus Anwendungsbereichen bei nicht tumorkranken Menschen gesicherte Daten über Qualität und Sicherheit dokumentiert sind und eine Übertragung solcher Daten auf die Situation tumorkranker Menschen unter kritischer Abwägung möglich erscheint. Phytotherapeutika spielen zudem in der Supportivtherapie eine zunehmende Rolle, wobei zahlreiche dieser Phytotherapeutika neben ihrer symptomatischen supportiven Wirksamkeit auch antiinflammatorische Wirkungen zeigen. Die gezielte Auswahl von supportiv wirksamen Phytotherapeutika mit zusätzlichen antiinflammatorischen Effekten könnte für tumorkranke Menschen neben der Symptomlinderung simultan die Möglichkeit einer antiinflammatorischen antitumoralen Wirksamkeit bieten als eine Art personalisierter Phytotherapie. Zurzeit besteht diesbezüglich noch ein groβer Bedarf an therapeutisch orientierter klinischer Forschung. Copyright © 2011 S. Karger AG, Base