Spontaneous tumors regression has been associated with microbial infection for 100s of years and inspired the use of bacteria for anticancer therapy. Dr. William B. Coley (1862–1936), a bone- sarcoma surgeon, was a pioneer in treating his patients with both live bacterial-based and mixture of heat-killed bacteria known as “Coley’s toxins.” Unfortunately, Coley was forced to stop his work which interrupted this field for about half a century. Currently, several species of bacteria are being developed against cancer. The bacterial species, their genetic background and their infectious behavior within the tumor microenvironment are thought to be relevant factors in determining their anti-tumor effectiveness in vivo. In this perspective article we will update the most promising results achieved using bacterial therapy (alone or combined with other strategies) in clinically-relevant animal models of cancer and critically discuss the impact of the bacterial variants, route of administration and mechanisms of bacteria-cancer-cell interaction. We will also discuss strategies to apply this information using modern mouse models, molecular biology, genetics and imaging for future bacterial therapy of cancer patients.

The antioxidant capacity of propolis from the southern region of Uruguay was evaluated using in vitro as well as cellular assays. Free radical scavenging capacity was assessed by ORAC, obtaining values significantly higher than those of other natural products (8000 μmol Trolox equiv/g propolis). ORAC values correlated well with total polyphenol content (determined by Folin-Ciocalteu method) and UV absorption. Total polyphenol content (150 mg gallic acid equiv/g propolis) and flavonoids (45 mg quercetin equiv/g propolis) were similar to values reported for southern Brazilian (group 3) and Argentinean propolis. Flavonoid composition determined by RP-HPLC indicates a strong poplar-tree origin. Samples high in polyphenols efficiently inhibit low-density lipoprotein lipoperoxidation and tyrosine nitration. In addition, Uruguayan propolis was found to induce the expression of endothelial nitric oxide synthase and inhibit endothelial NADPH oxidase, suggesting a potential cardiovascular benefit by increasing nitric oxide bioavailability in the endothelium.

BackgroundMetastatic breast cancer is a major cause of death among women worldwide; therefore efficient therapeutic strategies are extremely needed. In this work we have developed a gene therapy- and bacteria-based combined neoadjuvant approach and evaluated its antitumor effect in a clinically relevant animal model of metastatic breast cancer.Methods2×108 particles of a Semliki Forest virus vector expressing interleukin-12 (SFV-IL-12) and/or 2×107 units of an aroC− Samonella Typhimurium strain (LVR01) were injected into 4T1 tumor nodules orthotopically implanted in mice. Tumors were surgically resected and long-term survival was determined. IL-12 and interferon-γ were quantified by Enzyme-Linked ImmunoSorbent Assay, bacteria was visualized by inmunohistochemistry and the number of lung metastasis was calculated with a clonogenic assay.ResultsSFV-IL-12 and LVR01 timely inoculated and followed by surgical resection of tumors succeeded in complete inhibition of lethal lung metastasis and long-term survival in 90 % of treated mice. The combined therapy was markedly synergistic compared to each treatment alone, since SFV-IL-12 monotherapy showed a potent antiangiogenic effect, being able to inhibit tumor growth and extend survival, but could not prevent establishment of distant metastasis and death of tumor-excised animals. On the other hand, LVR01 alone also showed a significant, although limited, antitumor potential, despite its ability to invade breast cancer cells and induce granulocyte recruitment. The efficacy of the combined therapy depended on the order in which both factors were administered; inasmuch the therapeutic effect was only observed when SFV-IL-12 was administered previous to LVR01, whereas administration of LVR01 before SFV-IL-12 had negligible antitumor activity. Moreover, pre-treatment with LVR01 seemed to suppress SFV-IL-12 antiangiogenic effects associated to lower IL-12 expression in this group. Re-challenged mice were unable to reject a second 4T1 tumor; however 100 % of them could be totally cured by applying the same neoadjuvant combined regimen. To our knowledge, these are the most encouraging results obtained to date in a post-operatory setting using the highly aggressive 4T1 animal model.ConclusionsSFV-IL-12-based gene therapy combined with Salmonella LVR01 neoadjuvant administration has a synergic antitumor effect and may be a promising therapeutic option to prevent and/or eradicate pre-operatory metastasis in locally advanced breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1618-x) contains supplementary material, which is available to authorized users.

Human metapneumovirus (hMPV) has been described as circulating among the Uruguayan population at least since 1998 based on serologic evidence. However, no isolation attempts, molecular detection, or genetic studies have been carried out so far in the country. In the present study, molecular detection of circulating hMPV in children hospitalized with acute respiratory tract infection in Montevideo-Uruguay was carried out by reverse transcription-polymerase chain reaction (RT-PCR) amplification of the hMPV nucleoprotein (N) gene from 217 nasopharyngeal aspirates. Genetic variability analysis of the positive samples was performed by amplification and sequencing of both N and attachment glycoprotein (G) genes. Eighteen of the 217 samples tested positive for hMPV, with tachypnea, chest indrawing, and wheezing being the main clinical symptoms recorded. Phylogenetic analysis of N and G genes showed that Uruguayan samples clustered in genotypes described previously as A2, B1, and B2, with bootstrap values >or=98%. Sublineages A2a and A2b could also be distinguished within the samples that belong to A2. This is the first molecular report on the circulation of hMPV in Uruguay. The pattern of circulation of this virus, analyzed for both N and G genes independently, resembles the complex evolutionary pattern of respiratory syncytial virus (RSV).