Profile of Steroid Receptors and Increased Aromatase Immunoexpression in Canine Inflammatory Mammary Cancer as a Potential Therapeutic Target

Canine inflammatory mammary cancer (IMC) has been proposed as a model for the study of human inflammatory breast cancer (IBC). The aims of this study were to compare the immunohistochemical expression of aromatase (Arom) and several hormone receptors [estrogen receptor α (ERα), estrogen receptor β (ERβ), progesterone receptor (PR) and androgen receptor (AR)], in 21 IMC cases vs 19 non‐IMC; and to study the possible effect of letrozole on canine IMC and human inflammatory breast cancer (IBC) in vitro using IPC‐366 and SUM‐149 cell lines. Significant elevations of the means of Arom Total Score (TS), ERβ TS and PR TS were found in the IMC group (p = 0.025, p = 0.038 and p = 0.037, respectively). Secondary IMC tumours expressed higher levels of Arom than primary IMC (p = 0.029). Non‐IMC PR‐ tumours contained higher levels of Arom than non‐IMC PR+ tumours (p = 0.007). After the addition of letrozole, the number of IMC and IBC cells dropped drastically. The overexpression of Arom found and the results obtained in vitro further support canine IMC as a model for the study of IBC and future approaches to the treatment of dogs with mammary cancer, and especially IMC, using Arom inhibitors.     

Effect of pharmacological concentrations of zinc oxide with or without the inclusion of an antibacterial agent on nursery pig performance

A study involving nine research stations from the NCR-42 Swine Nutrition Committee used a total of 1,978 crossbred pigs to evaluate the effects of dietary ZnO concentrations with or without an antibacterial agent on postweaning pig performance. In Exp. 1, seven stations (IA, MI, MN, MO, NE, ND, and OH) evaluated the efficacy of ZnO when fed to nursery pigs at 0, 500, 1,000, 2,000, or 3,000 mg Zn/kg for a 28-d postweaning period. A randomized complete block experiment was conducted in 24 replicates using a total of 1,060 pigs. Pigs were bled at the 28-d period and plasma was analyzed for Zn and Cu. Because two stations weaned pigs at < 15 d (six replicates) and five stations at > 20 d (18 replicates) of age, the two sets of data were analyzed separately. The early-weaned pig group had greater (P < 0.05) gains, feed intakes, and gain:feed ratios for the 28-d postweaning period as dietary ZnO concentration increased. Later-weaned pigs also had increased (P < 0.01) gains and feed intakes as the dietary ZnO concentration increased. Responses for both weanling pig groups seemed to reach a plateau at 2,000 mg Zn/kg. Plasma Zn concentrations quadratically increased (P < 0.01) and plasma Cu concentrations quadratically decreased (P < 0.01) when ZnO concentrations were > 1,000 mg Zn/kg. Experiment 2 was conducted at seven stations (KY, MI, MO, NE, ND, OH, and OK) and evaluated the efficacy of an antibacterial agent (carbadox) in combination with added ZnO. The experiment was a 2 x 3 factorial arrangement in a randomized complete block design conducted in a total of 20 replicates. Carbadox was added at 0 or 55 mg/kg diet, and ZnO was added at 0, 1,500, or 3,000 mg Zn/ kg. A total of 918 pigs were weaned at an average 19.7 d of age. For the 28-d postweaning period, gains (P < 0.01), feed intakes (P < 0.05), and gain:feed ratios (P < 0.05) increased when dietary ZnO concentrations increased and when carbadox was added. These responses occurred in an additive manner. The results of these studies suggest that supplemental ZnO at 1,500 to 2,000 mg Zn/kg Zn improved postweaning pig performance, and its combination with an antibacterial agent resulted in additional performance improvements.     

Matrix metalloproteinase-2 and -9 are activated in joint diseases.

A study was performed to identify the activation status of the gelatinase MMPs, MMP-2 and -9, in both normal and diseased equine articular tissues. In addition, the production and activation status of equine MMP-2 and -9 by equine articular cells and tissues in response to increasing IL-1beta concentrations was assessed. The study was performed to test the hypothesis that activation of MMPs is a fundamental step in the pathogenesis of joint diseases; and that this activation is mediated by the cytokine IL-1. Using purified equine MMP-2 and -9, the molecular weights of the zymogen and activated form of equine MMP-2 and -9 were identified by a combination of gelatin zymography and a gelatin degradation assay using aminophenylmercuric acetate as a chemical activator of the molecules. Normal equine articular tissues (cartilage and synovial membrane) maintained in short-term tissue culture produced MMP-2 zymogen alone, while similar tissues obtained from a variety of pathological conditions produce both zymogen and active MMP-2, as well as MMP-9 monomer and dimer. Activated MMP-9 was an inconsistent finding. Normal equine synovial fibroblasts in monolayer culture produced zymogen MMP-2 alone under basal conditions. A mild increase in active and zymogen MMP-2 levels occurred with IL-1beta treatment. Equine synovial membrane explants demonstrated a dose-dependent increase in active and zymogen MMP-2 and MMP-9 levels following IL-1beta treatment. Monolayer chondrocyte cell cultures demonstrated a dose-dependent mild increase in active and zymogen MMP-2 following IL-1beta treatment. Explant cartilage cultures demonstrated a dose-dependent mild increase in zymogen MMP-2 alone following IL-1beta treatment. This study supports the hypothesis that activation of MMPs is occurring in joint disease, and that in vitro stimulation of equine articular cells and tissues causes not only an increase in MMP production, but also an increase in amount of activated enzyme released. Further research is required to investigate the role of MMP activation in joint diseases, and to investigate the potential use of therapeutic agents, which inhibit MMP activation, in the treatment and prevention of joint diseases.