Evaluation of adjuvant doxorubicin-based chemotherapy for the treatment of feline mammary carcinoma.

BACKGROUND: Feline mammary carcinomas (FMC) are locally invasive and highly metastatic tumors. Because of the high metastatic potential, patients often are treated with adjuvant doxorubicin-based chemotherapy, but little data exist to evaluate the effect of this strategy. HYPOTHESIS: Adjuvant doxorubicin-based chemotherapy improves outcome for FMC compared with surgery alone. ANIMALS: Cats with naturally occurring, biopsy-confirmed FMC treated with either surgery alone (Sx) or with surgery plus adjuvant doxorubicin-based chemotherapy (Sx + Chemo). METHODS: Retrospective cohort study. Clinical data were collected and compared to identify differences between groups. Outcome results were determined and compared. Prognostic factors for disease-free survival (DFS) and overall survival were evaluated. RESULTS: Seventy-three cats were evaluated, of which 37 were in the Sx group and 36 in the Sx + Chemo group. No differences in clinical data were found between Sx and Sx + Chemo groups. Median DFS times for the Sx and Sx + Chemo groups were 372 and 676 days, respectively (P= .15) and median survival times (ST) were 1,406 and 848 days, respectively (P= .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx + Chemo compared with the Sx group (1,998 versus 414 days, respectively; P= .03). CONCLUSIONS AND CLINICAL IMPORTANCE: This study did not find a benefit to adjuvant doxorubicin-based chemotherapy in cats with FMC. Additional studies are required to determine whether patient subgroups with negative prognostic factors may benefit from adjuvant chemotherapy.

Characterization of the biological behaviour of appendicular osteosarcoma in Rottweilers and a comparison with other breeds: a review of 258 dogs.

The purpose of this retrospective study was to compare Rottweilers diagnosed with osteosarcoma (OSA) with other breeds to determine whether Rottweilers experienced a more aggressive form of the disease. Two hundred and fifty-eight dogs were evaluated (102 clinical and 156 necropsy cases). In the necropsy population, Rottweilers had a younger mean age at death (7.3 versus 9 years, P = 0.006). There were no significant differences between Rottweilers and other breeds in age at diagnosis, median disease-free interval or survival time. However, Rottweilers were more likely to have metastasis to the brain (7 versus 0%, P = 0.03). These results suggest that OSA in Rottweilers may have a different biological behaviour, but this study did not confirm that these differences were associated with a worse outcome.

Expression and activity of transglutaminase II in spontaneous tumours of dogs and cats.

Tissue transglutaminase II (TGase II) is a dual function protein with both transamidating and guanidine triphosphate (GTP)-binding capabilities. Previous studies have implicated TGase as a pro-apoptotic molecule; however, our recent findings indicate that TGase II may act as a survival factor in various cell types. The purpose of this study was to survey TGase II expression in normal tissue and spontaneous tumours of dogs and cats, by Western blotting and immunohistochemistry. Bladder, liver and adrenal gland exhibited prominent expression of TGase II while other tissues, including mammary gland, displayed limited expression and activity. TGase II GTP-binding in normal tissues was proportional to the level of expression in all tissues examined. Normal mammary tissue and that showing benign hyperplasia did not express TGase II. However, 11/25 (44%) of canine mammary carcinomas and 10/12 (83%) of feline mammary carcinomas strongly expressed TGase II in either a stromal, cellular or combined pattern. The pattern of expression was not related to the classification of mammary carcinoma (solid, tubulopapillary, complex or anaplastic), except that two anaplastic canine mammary carcinomas showed prominent TGase II expression. Two canine mammary carcinoma cell lines showed prominent TGase expression, and when the TGase activity was inhibited, the cells became more sensitive to doxorubicin-induced cell death. Thus, TGase II was significantly expressed in mammary cancers from dogs and cats and immunoreactivity of TGase II was similar to that reported in humans beings. The pro-survival effect of TGase II in canine mammary carcinoma cell lines was similar to that previously reported in humans patients.

Fluoride release from new light-cured orthodontic bonding agents.

The purpose of this study was to compare the rates of fluoride release with time from 1 nonfluoridated and 3 fluoride-containing orthodontic bonding materials in distilled water and artificial saliva. Materials tested were Assure (Reliance Orthodontic Products, Itasca, Ill), Fuji Ortho LC (GC, Tokyo, Japan), Python (TP Orthodontics, LaPorte, Ind), and Transbond XT (3M Dental Products, Monrovia, Calif). Ten specimens of each material type were stored in distilled water, and 10 of each type were stored in artificial saliva at 37 degrees C. Fluoride release was measured with an ion-specific electrode. Readings were taken periodically for a total time period of 6 months. At day 1, Assure released the most fluoride into distilled water (66.2 microg/cm(2)) and into artificial saliva (65.8 microg/cm(2)), followed by Fuji Ortho LC (25.9 microg/cm(2); 18.8 microg/cm(2)), Python (6.3 microg/cm(2); 4.2 microg/cm(2)), and Transbond (0.1 microg/cm(2); 0.1 microg/cm(2)). The fluoride release rates were highest during the first days of testing, declining to lower but more stable levels. At the end of 6 months, Fuji Ortho LC released the most fluoride (3.8 microg/cm(2); 3.5 microg/cm(2)) followed by Assure (3.1 microg/cm(2); 2.8 microg/cm(2)), Python (2.6 microg/cm(2); 1.7 microg/cm(2)), and Transbond (0.1 microg/cm(2); 0.1 microg/cm(2)). The type of storage medium did not dramatically affect fluoride release. The second part of the study, undertaken after a year of sample storage, tested the 20 samples of Assure for a further 2-week period, after exposure to running and still distilled water. Although fluoride release rates declined with time, they were still higher than the 1.5 microg/cm(2) level that is referenced as inhibiting decalcification of enamel in a clinical environment. Release rates were similar in running and still water at all time points. Throughout the 6-month period, all 3 fluoride-containing materials had rates of fluoride release that could theoretically inhibit decalcification of enamel.

Dietary lipid modulation of immune responsiveness.

The influence of dietary fat concentration and saturation on blastogenesis, cytotoxicity, antibody response and fatty acid composition of murine splenic lymphocytes was studied. Blastogenesis of lymphocytes from dietarily manipulated mice in response to alloantigens from control mice was significantly greater for those mice fed a diet containing minimal essential fatty acids (EFA) as the only fat source (EFA control) than those fed an EFA-deficient diet. When the dietary fat concentration was increased, blastogenic response decreased compared to the EFA control diet. Lymphocyte-mediated cytotoxicity against allogeneic melanoma cells was greater for mice receiving diets with EFA only than for those deficient in EFA. However, cytotoxicity responses of mice fed additional polyunsaturated fat (PUF) decreased as concentration increased, whereas responses of mice fet the saturated fat (SF) diets decreased only when the dietary fat concentration was greater than 8%. As compared to diets with EFA control, direct plaque-forming cell (PFC) response was decreased for mice fed high levels of PUF and increased for mice fed high levels of SF; however, no difference in the percentage of IgM-positive cells was observed. These changes in PFC response were inversely related to the levels of linoleic acid in the lymphocyte. Thus, high levels of dietary fat, and particularly PUF, suppress lymphocyte functions when EFA requirements are met, whereas low levels (EFA control) intensify these responses. EFA deficiency, however, suppress some lymphocyte responses. Thus, dietary lipids differentially modulate the levels of T- and B-cell responsiveness.

Influence of dietary fat concentration and saturation on immune ontogeny in mice.

Dietary fat modulation of immune responsiveness was studied using a murine model subjected to prenatal and postnatal dietary manipulation. The weight of lymphoid associated organs, particularly the spleen, thymus and liver were significantly influenced by dietary fat saturation and concentration whereas other organs studied were not influenced by this manipulation. The serum immunoglobulins IgG1 and IgG2, but not IgM or IgA, increased in mice fed the polyunsaturated fat (PUF) diet as compared to the levels in those mice fed the saturated fat (SF) diet. While dietary manipulation generally did not influence the peripheral differential blood cell counts, the percentage of immunoglobulin positive splenic cells changed with dietary manipulation; the percentage of T cells, however, was not influenced by the experimental diets. In contrast, T-cell blastogenesis was influenced by both saturation and concentration of dietary fat whereas B-cell transformation was influenced by neither variable. Changes in T-cell responses were manifested through changes in the lymphocytes, and not cell numbers; PUF, particularly high levels, suppresses lymphocyte blastogenesis whereas low levels or a deficiency of PUF intensify this response. It is concluded that dietary fats influence the modulation and level of immune function.

Effects of low dietary protein concentration and energy deprivation on lymphocyte transformation in melanoma-bearing mice.

Temporal changes in lymphocyte blastogenesis were studied using spleen cells from syngeneic melanoma-bearing and control mice fed various levels of purified diets containing 6, 10 or 30% casein. T-cell blastogenesis was stimulated by the presence of the tumor and these responses changed with the duration of feeding. In addition, protein concentration did not affect T-cell transformation but the level of energy intake influenced concanavalin A induced DNA synthesis. In contrast, the growing melanoma did not influence B-cell transformation whereas a very low level of dietary protein, a low level of energy intake and duration of the dietary manipulation influenced these cells. Tumor weights were generally not affected by the diet except in mice receiving a very low level of energy intake. Thus, we have found that B-cell responses were affected more than those of T-cells and that moderate protein deficiency did not enhance cellular immune responses in syngeneic tumor-bearing and control mice.