Septic Peritonitis Secondary to Neoplasia in Two Canine Cancer-Bearing Patients Lacking Gastrointestinal and Hepatic Organ Rupture.

In this case report, we describe the presentation, diagnosis, and outcome of septic peritonitis secondary to neoplasia in patients lacking evidence of gastrointestinal content leakage, liver abscessation, or other treatment-associated risk factors. Two dogs presented with a diagnosis of neoplasia and nonspecific clinical signs such as lethargy, hyporexia, vomiting, and discomfort that was localized to the abdomen. The diagnoses at presentation consisted of a perianal tumor consistent with apocrine gland anal sac adenocarcinoma and systemic mastocytosis. Neither of the dogs was considered systemically immunocompromised or had received recent cytotoxic chemotherapy treatment or surgical procedures. A common finding on blood work in the two dogs was the presence of band neutrophils. The diagnosis of septic peritonitis via fluid analysis and cytology was delayed in both cases. No treatment for the supposed underlying cause of septic peritonitis was pursued and euthanasia was pursued in both cases owing to poor prognosis. On necropsy, one dog was suspected to have developed septic peritonitis because of an abscessed lymph node, and in the other case, no definitive source was identified. Septic peritonitis can arise secondary to neoplasia that is not primarily involving the liver or gastrointestinal tract in canine patients that lack treatment-associated risk factors.

Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development.

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qß. Mouse immunization with the Qß-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qß-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

Skin depigmentation associated with toceranib phosphate in a dog.

BACKGROUND: Drug-induced depigmentation is frequently observed in humans undergoing tyrosine kinase inhibitor therapy, whereas it is not reported in dogs. The skin depigmentation can occur after the first week of treatment and it is reversible within a few weeks after drug discontinuation. OBJECTIVES: To report the clinical and histopathological features of an episode of cutaneous adverse drug reaction associated with short term administration of toceranib phosphate. CASE REPORT: An 11-year-old intact male Bernese mountain dog was presented for investigation of a subcutaneous mast cell tumour (MCT) including treatment options. The major abnormality on physical examination was a 7.5 × 10 cm subcutaneous mass located cranial to the left shoulder joint consistent with a MCT. Toceranib phosphate therapy was initiated. Fourteen days after initiating treatment, the dog presented with skin erosions near the lateral canthus of the left eye. Three weeks later there were multiple skin lesions characterized by alopecia and depigmentation involving left and right eyelids; leukotrichia of the periorbital areas and depigmentation of the nasal planum and all paw pads. Histopathological findings were nonspecific; they were supportive of vitiligo. Resolution of skin lesions was observed after stopping the toceranib phosphate therapy. CONCLUSION AND CLINICAL IMPORTANCE: Based on the gross lesions, histopathological features before and after tyrosine kinase inhibitor therapy, and Naranjo score, this case was considered to be consistent with cutaneous adverse drug effects. To the best of the authors' knowledge, this is the first report describing the clinical and histopathological features of presumed drug-induced skin depigmentation in a dog receiving toceranib phosphate.

Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials.

Ninety percent of deaths from cancer are caused by metastasis. miRNAs are critical players in biological processes such as proliferation, metastasis, apoptosis, and self-renewal. We and others have previously demonstrated that miRNA-10b promotes metastatic cell migration and invasion. Importantly, we also showed that miR-10b is a critical driver of metastatic cell viability and proliferation. To treat established metastases by inhibiting miR-10b, we utilized a therapeutic, termed MN-anti-miR10b, composed of anti-miR-10b antagomirs, conjugated to iron oxide nanoparticles, that serve as delivery vehicles to tumor cells in vivo and a magnetic resonance imaging (MRI) reporter. In our previous studies using murine models of metastatic breast cancer, we demonstrated the effectiveness of MN-anti-miR10b in preventing and eliminating existing metastases. With an outlook toward clinical translation of our therapeutic, here we report studies in large animals (companion cats) with spontaneous feline mammary carcinoma (FMC). We first investigated the expression and tissue localization of miR-10b in feline tumors and metastases and showed remarkable similarity to these features in humans. Next, in the first case study involving this therapeutic we intravenously dosed an FMC patient with MN-anti-miR10b and demonstrated its delivery to the metastatic lesions using MRI. We also showed the initial safety profile of the therapeutic and demonstrated significant change in miR-10b expression and its target HOXD10 after dosing. Our results provide support for using companion animals for further MN-anti-miR10b development as a therapy and serve as a guide for future clinical trials in human patients.

Expression of the Bcl-2 apoptotic marker in cats diagnosed with inflammatory bowel disease and gastrointestinal lymphoma.

Immunolabeling for the critical lymphocyte survival factor, Bcl-2, of intestinal biopsies from cats with histologic evidence of inflammatory bowel disease (IBD) or gastrointestinal (GI) lymphoma was evaluated to determine if expression differed significantly between these two disease processes. Immunolabeling for Bcl-2 was performed on small intestinal endoscopic or full thickness biopsy sections from 55 cats. Diagnosis of IBD, T-cell lymphoma or B-cell lymphoma was established previously. The percentage of infiltrating lymphocytes that were positively labeled for Bcl-2 was subjectively determined for each case. Eight cats were diagnosed with IBD and 47 cats with lymphoma. A significantly higher percentage of cells were positively immunolabeled for Bcl-2 in cats with GI lymphoma [median (range); 90 (5-95)%] compared with cats with IBD [60 (15-95)%] (P = 0.029). However, the overall degree of positive immunolabeling in both groups tended to be high. This over-expression of Bcl-2 may prove useful as a therapeutic target for IBD and GI lymphoma in cats.