The purpose of this study was to provide an initial assessment of the potential biologic activity of toceranib phosphate (Palladia®) in select solid tumors in dogs. Cases in which toceranib was used to treat dogs with anal sac anal gland adenocarcinoma, metastatic osteosarcoma, thyroid carcinoma, head and neck carcinoma, and nasal carcinoma were included. Clinical benefit (CB) was observed in 63/85 (74%) dogs including 28/32 anal sac tumors (8PR, 20SD), 11/23 osteosarcomas (1PR, 10SD), 12/15 thyroid carcinomas (4PR, 8SD), 7/8 head and neck carcinomas (1CR, 5PR, 1SD) and 5/7 (1CR, 4SD) nasal carcinomas. For dogs experiencing CB, the median dose of toceranib was 2.8 mg/kg, 36/63 (58.7%) were dosed on a Monday/Wednesday/Friday basis, and 47/63 (74.6%) were treated 4 months or longer. While these data povide preliminary evidence that toceranib exhibits CB in dogs with certain solid tumors, future prospective studies are necessary to define its true activity.

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 1 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 1 Chemo group. No differences in clinical data were found between Sx and Sx 1 Chemo groups. Median DFS times for the Sx and Sx 1 Chemo groups were 372 and 676 days, respectively (P 5 .15) and median survival times (ST) were 1,406 and 848 days, respectively (P 5 .78). For cats that underwent a unilateral radical mastectomy, ST was significantly longer for the Sx 1 Chemo compared with the Sx group (1,998 versus 414 days, respectively; P 5 .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.

Retinoic acid (RA) is a potent activator of tissue transglutaminase (TGase) expression, and it was recently shown that phosphoinositide 3-kinase (PI3K) activity was required for RA to increase TGase protein levels. To better understand how RA-mediated TGase expression is regulated, we considered whether co-stimulation of NIH3T3 cells with RA and epidermal growth factor (EGF), a known activator of PI3K, would facilitate the induction or increase the levels of TGase expression. Instead of enhancing these parameters, EGF inhibited RA-induced TGase expression. Activation of the Ras-ERK pathway by EGF was sufficient to elicit this effect, since continuous Ras signaling mimicked the actions of EGF and inhibited RA-induced TGase expression, whereas blocking ERK activity in these same cells restored the ability of RA to up-regulate TGase expression. However, TGase activity is not antagonistic to EGF signaling. The mitogenic and anti-apoptotic effects of EGF were not compromised by TGase overexpression, and in fact, exogenous TGase expression promoted basal cell growth and resistance to serum deprivation-induced apoptosis. Moreover, analysis of TGase expression and GTP binding activity in a number of cell lines revealed high basal TGase GTP binding activity in tumor cell lines U87 and MDAMB231, indicating that constitutively active TGase may be a characteristic of certain cancer cells. These findings demonstrate that TGase may serve as a survival factor and RA-induced TGase expression requires the activation of PI3K but is antagonized by the Ras-ERK pathway.

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.

Feline small cell lymphoma is associated with greater response to treatment and survival when compared to large cell lymphoma. Treatment‐associated toxicity, response to rescue chemotherapy and prognostic factors are largely unknown. This retrospective study was performed to identify treatment‐associated toxicity, response to rescue chemotherapy and treatment outcome for cats diagnosed with small cell lymphoma of various anatomic locations. Medical records from 56 cats were evaluated. All cats were treated with glucocorticoid and chlorambucil with discontinuation of treatment recommended at 1 year if complete clinical response was documented. Chemotherapy toxicity was uncommon (33.9%) and generally mild. Grade III or IV hepatotoxicity was documented in 10.7% of patients. Overall response rate was 85.7% with glucocorticoid and chlorambucil. Median progression‐free survival was 1078 days. Overall response rate for rescue chemotherapy was 59%. Reintroduction of prednisone and chlorambucil was associated with significantly longer survival than prednisone and lomustine (>1500 vs. 492 days, P = 0.01). Median overall survival times for cats with lymphoma of the gastrointestinal tract was not significantly different from those with extra‐intestinal disease locations (1148 vs. 1375 days, P = 0.23). Median overall survival was 1317 days. Toxicity, other than hepatotoxicity was mild. Rescue chemotherapy with re‐introduction of glucocorticoids and chlorambucil was most successful. Discontinuation of glucocorticoid and chlorambucil with subsequent reintroduction as rescue chemotherapy appears to be just as effective as continued administration in cats.