To determine whether the c-Ha-ras oncogene plays a role in the initiation of mammary carcinogenesis, an immortalized human breast epithelial cell line, MCF-10A, was transfected with the plasmid vector pHo6T1 containing the T24 Ha-ras oncogene and the aminoglycoside phosphotransferase gene, which confers resistance to geneticin. Transfected cells exhibited an altered pattern of growth and tridimensional morphology in collagen gel. They also exhibited anchorage-independent growth and loss of requirement for hormones and epidermal growth factor; in addition, they expressed invasiveness and increased collagenolytic activity in an in vitro system and became tumorigenic in irradiated nude mice, all properties indicative of malignant transformation. Transformed cells contained the mutated c-Ha-ras oncogene and expressed the p21 mutated protein. These data indicate that the c-Ha-ras oncogene is capable of inducing malignant phenotypes in immortalized human breast epithelial cells.

Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco-regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present.

The aim of the study was to report the outcome of treatment of 97 dogs with lymphoma that received a multi-agent chemotherapy protocol containing epirubicin as the primary anthracycline. Seventy-five dogs received a 25-week protocol with no maintenance phase whilst 22 dogs received a maintenance phase. Complete response rate was 96% and time to first relapse (TTR) and overall survival (OS) time for all dogs were 216 and 342 days, respectively. Dogs with T-cell lymphoma and those classified as WHO substage b had significantly poorer OS times and TTR. The protocol was well tolerated with toxicity similar to doxorubicin-containing protocols. Epirubicin as part of a multi-agent protocol is safe and effective in the treatment of canine multicentric lymphoma. There is a high initial response rate and an overall median survival time that is similar to other published doxorubicin-containing protocols.

T-lymphocyte development takes place mainly in the thymus, where stromal cells of epithelial and haemopoietic origin are involved in inductive and selective mechanisms, which enable specific lymphocyte populations to migrate to the periphery and establish a network of immune responses. Experiments with intact animals have clarified the precursor-product relationships between thymocyte subpopulations, but the molecular mechanisms of cell interactions in the thymus are difficult to study in vivo. In an attempt to expand thymic cell populations in vivo and maintain them in vitro for such studies, we directed high levels of expression of the murine c-myc proto-oncogene in transgenic mice by inserting it into the mouse Thy-1 transcriptional unit. Such mice develop thymic tumours which contain proliferating thymocytes and, interestingly, expanded populations of epithelial cells. Both cell types can be maintained in vitro.

OBJECTIVE To assess response and outcome in dogs with stage 4 anal sac apocrine gland adenocarcinoma (ASAGA) treated with toceranib phosphate as the sole chemotherapeutic agent. DESIGN Retrospective case series. ANIMALS 15 client-owned dogs with stage 4 ASAGA treated with toceranib phosphate between March 2013 and June 2017. PROCEDURES Medical records were reviewed, and data collected included signalment, clinical signs, results of physical examinations and diagnostic procedures, treatments, response, follow-up information, and outcomes. Adverse events and response to treatment were assessed according to standard guidelines, and the Kaplan-Meier product limit method was used for analyses of progression-free interval and survival time. RESULTS No dogs had a complete or partial response to treatment with toceranib; however, 13 dogs had signs of clinical benefit. No dogs had signs of toxic effects related to toceranib or were withdrawn completely from treatment because of adverse events. Median progression-free interval and median survival time were 354 and 356 days, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Results of the present study indicated that dogs with stage 4 ASAGA treated with toceranib had improved outcomes, compared with outcomes previously reported for dogs with ASAGA that had received non–tyrosine kinase inhibitor treatments. Some dogs had improvement in clinical signs, but euthanasia was often performed because of signs of locoregional failure; therefore, toceranib alone may not be an appropriate treatment for dogs with marked clinical signs attributed to ASAGA, particularly when signs suggest limited quality of life. Further study of toceranib in multimodality treatments for dogs with advanced ASAGA is warranted.