Auranofin improves overall survival when combined with standard of care in a pilot study involving dogs with osteosarcoma

Osteosarcoma is the most common paediatric primary bone malignancy. The major cause of death in osteosarcoma is drug‐resistant pulmonary metastasis. Previous studies have shown that thioredoxin reductase 2 is a driver of metastasis in osteosarcoma and can be inhibited by auranofin (AF). Moreover, studies have shown that AF significantly reduces pulmonary metastases in xenotransplant models. Here, we describe a phase I/II study of AF in canine osteosarcoma, a well‐recognized spontaneous model of human osteosarcoma. We performed a single‐arm multicentre pilot study of AF in combination with standard of care (SOC) (amputation + carboplatin). We recruited 40 dogs to the trial and used a historical SOC‐only control group (n = 26). Dogs >15 kg received 9 mg AF q3d PO and dogs <15 kg received 6 mg q3d. Follow‐up occurred over at least a 3‐year period. Auranofin plus SOC improved overall survival (OS) (P = .036) in all dogs treated. The improved outcome was attributable entirely to improved OS in male dogs (P = .009). At the time of writing, 10 dogs (25%) survive without measurable disease in the treatment group with survival times ranging between 806 and 1525 days. Our study shows that AF improves OS in male dogs when combined with SOC. Our findings have translational relevance for the management of canine and human osteosarcoma. Our data justify a larger multicentre phase 2 trial in dogs and a phase I/II trial in human patients with refractory disease at the time of initial surgery.     

Analysis of domestic animal movements in Colombia (2006–2014) and their possible influence on the bovine brucellosis spread

Tropical Animal Health and Production - Bovine brucellosis is a zoonotic disease that causes great economic losses. The disease is endemic in Colombia and animal movements from infected herds carry...     

Results of a web-based health survey of retired racing Greyhounds

BACKGROUND: Adoption of retired racing Greyhounds has become increasingly popular during the past decade. To date, research has focused on the physiologic and clinicopathologic peculiarities of Greyhounds but there is little published information on disease prevalence in the breed. OBJECTIVE: The objective of this study is to determine the prevalence of disease in retired racing Greyhounds. ANIMALS: In this study, 747 Greyhounds were used. METHODS: A standardized survey method was used, and survey responses were collected by an Internet survey. Owners could answer a survey for every Greyhound that they had owned since January 1, 2005. RESULTS: Of the 692 eligible participants, 441 (63.7% response rate) completed surveys for 747 Greyhounds. The mortality rate for Greyhounds within the 2-year period was 15% (113 of 747 died). The most common cause of death reported was cancer (66 dogs, 58%), and the most common type of cancer listed as the cause of death was osteosarcoma (28 dogs, 25%). The most commonly reported groups of diseases or disorders were skeletal (232 dogs, 33%), skin (197 dogs, 28%), digestive (132 dogs, 18%), cancer (94 dogs, 13%), and endocrine (85 dogs, 11.9%). Forty-five percent of Greyhounds diagnosed with cancer and 6% of the overall population had osteosarcoma. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study can be used by veterinary researchers to continue to investigate the most common diseases in this population. As more retired racing Greyhounds enter the pet population, the results of this study will help educate veterinarians and owners about the most prevalent diseases in the breed.     

Variant-specific and diminishing immune responses towards the highly variable MSP2(P44) outer membrane protein of Anaplasma phagocytophilum during persistent infection in lambs

Anaplasma phagocytophilum is the causative agent of tick-borne fever in small ruminants and has been identified as the zoonotic agent of human granulocytic anaplasmosis. The Norwegian strains of the rickettsia are naturally persistent in lambs and represent a suitable experimental system for analyzing the mechanisms of persistence. Variation of the outer membrane protein MSP2(P44) by recombination of variable pseudogene segments into an expression site is believed to play a key role in persistence of the organism. The goal of the present study was to analyze the dynamics of the immune response towards A. phagocytophilum and MSP2(P44) during persistent infection of lambs. Responses to the hypervariable region of MSP2(P44) were detected shortly after appearance of the respective variants in cyclic rickettsemic peaks, consistent with a process of antigenic variation. In addition, there was a diminishing antibody response to MSP2(P44) and to other A. phagocytophilum antigens overall with time of infection, that was not associated with clearance of the infection.     

Validating models of one-way land change: an example case of forest insect disturbance

Landscape Ecology - Validation of models of Land Use and Cover Change often involves comparing maps of simulated and reference change. The interpretation of differences between simulated and...     

A new natural spiro heterocyclic compound and the cytotoxic activity of the secondary metabolites from Juniperus brevifolia leaves

A new natural spiro compound 3,4-dehydrotheaspirone and the known arctiol [1β,6α-dihydroxy-4(14)-eudesmene] were isolated from Juniperus brevifolia. Arctiol is reported for the first time in the Juniperus genus. Their structures were established by 1D, and 2D NMR and MS spectra. Antimicrobial and cytotoxic activities of 1 and several secondary metabolites ,,,,,,,,, previously isolated by our group from J. brevifolia were evaluated and some SAR has been established. The 18-hydroxydehydroabietane (4) displayed great antiproliferative activity against cancer cell lines tested, namely HeLa, A-549 and MCF-7. Compound 4 also presented a significant bactericidal effect against Bacillus cereus at different concentrations tested.     

Effect of cutting age and substrate temperature on rooting of <Emphasis Type="Italic">Taxus globosa</Emphasis>

Taxus globosa (Mexican yew) is a conifer endemic to México and Central America. It produces a substance known as taxol, which is useful in treatment of ovarian cancer. Because seed production for this dioecious tree is limited, and seed germination is extremely difficult, the use of cuttings could facilitate propagation of this species. With the intention of massively propagating individuals selected for taxol content, two trials were established in which the effect of substrate temperature (average temperatures 18 and 23°C), age (i.e., young vs. old shoots) and management of cuttings, as well as clone variation in rooting capacity, were evaluated. Low temperature favored rooting (53 vs. 34% on average for the two trials); younger shoots rooted three times (61 vs. 23%) more than mature ones, while basal wounding did not affect rooting capacity. A wide variation was found in rooting capacity of clones (8–76%), which could be associated with genetic or physiological differences among donor trees.     

Characterization of aflatoxigenic and non-aflatoxigenic strains of <Emphasis Type="Italic">Aspergillus</Emphasis> section <Emphasis Type="Italic">Flavi</Emphasis> isolated from corn grains of different geographic origins in Brazil

Aflatoxins can cause great economic losses and serious risks to humans and animals health. The largest aflatoxin producers belong to Aspergillus section Flavi and can occur naturally in food commodities. Studies showed that molecular tools as well as the type of sclerotia produced by the strains could be helpful for identification of Aspergillus species and could be correlated with levels of toxin production. The purpose of this work was to characterize the genetic diversity using AFLP technique, the type of sclerotia and the ability of aflatoxin production by isolated strains from corn of different origins in Brazil, and to verify whether qPCR based on aflR and aflP genes is appropriate for estimating the level of aflatoxin production. All the 75 strains were classified as A. flavus and the AFLP technique showed a wide intraspecific variability within them. Regarding sclerotia production, 34% were classified as S and 66% as L type. Among the aflatoxin-producers, 52.8% produced aflatoxin B₁, while 47.2% aflatoxins B₁ and B₂. Statistical analysis showed no correlation between sclerotia production and aflatoxigenicty, and no correlation between the phylogenetic clusters and aflatoxin production. Concerning the relative expression of aflR and aflP, Pearson’s correlation test demonstrated low positive correlation between the expression of the aflR and aflP genes and the production of AFB₁ and AFB₂, but showed high positive correlation between aflR and aflP expression. In contrast to the other reference strains, A. oryzae ATCC 7282 showed no amplification of aflR and aflP. The results highlight the need for detection of reliable and reproducible markers with a high positive correlation with aflatoxin production.