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Developing effective therapies for the treatment of advanced head-and-neck squamous cell carcinoma (HNSCC) remains a major challenge, and there is a limited landscape of effective targeted therapies on the horizon. NAD(P)H:quinone oxidoreductase 1 (NQO1) is a 2-electron reductase that is overexpressed in HNSCC and presents as a promising target for the treatment of HNSCC. Current NQO1-targeted drugs are hindered by their poor oxidative tolerability in human patients, underscoring a need for better preclinical screening for oxidative toxicities for NQO1-bioactivated small molecules. Herein, we describe our work to include felines and feline oral squamous cell carcinoma (FOSCC) patients in the preclinical assessment process to prioritize lead compounds with increased tolerability and efficacy prior to full human translation. Specifically, our data demonstrate that IB-DNQ, an NQO1-targeted small molecule, is well-tolerated in FOSCC patients and shows promising initial efficacy against FOSCC tumors in proof-of-concept single agent and radiotherapy combination cohorts. Furthermore, FOSCC tumors are amenable to evaluating a variety of target-inducible couplet hypotheses, evidenced herein with modulation of NQO1 levels with palliative radiotherapy. The use of felines and their naturally-occurring tumors provide an intriguing, often underutilized tool for preclinical drug development for NQO1-targeted approaches and has broader applications for the evaluation of other anticancer strategies.

Sertoli cell tumours are one of the most common canine testicular neoplasia. These tumours are significantly more likely to arise in cryptorchid dogs and are often functional, oestrogen-secreting tumours which can lead to fatal myelotoxicity. The goal of this study was to describe the outcome of dogs with oestrogen-induced bone marrow suppression secondary to Sertoli cell tumours in seven client-owned dogs. Medical records from April 1, 2011 through April 1, 2021 were reviewed to identify dogs that underwent surgical management of a Sertoli cell tumour with documented bone marrow suppression. Overall, 5/7 dogs required transfusion of blood products peri-operatively. Cases 1 and 6 received a transfusion of packed red blood cells (RBC) prior to surgery and case 5 required a transfusion of whole blood. Case 1 also required a transfusion of platelets before surgery. Post-operatively, cases 1 and 2 received packed RBC's and case 6 received two transfusions of whole blood. Case 3 required transfusions of both fresh frozen plasma and platelets post-operatively. All dogs survived to discharge and 6/7 dogs had documented improvement in haematopoietic values. Two dogs remained chronically thrombocytopenic. The median hospital stay was 4 days. One dog died within 4 weeks of surgery from worsening pancytopenia. Survival for greater than 1 year was documented in 4/7 dogs, and one dog was lost to follow-up 4 months post-operatively. One dog remained severely pancytopenic 4 weeks post-operatively and received oral lithium treatment. Improvements in all blood cell lines were observed within the 4 weeks and resolution of pancytopenia within 6 weeks. Historically, the prognosis for dogs with bone marrow suppression secondary to Sertoli cell tumours was guarded to poor. This report documented improved outcomes for dogs that underwent surgery, including one dog that received lithium chloride as treatment for Sertoli cell tumour-induced bone marrow suppression.

The purpose of this report was to discuss the diagnosis, treatment, and outcome of a cat with an orbital lacrimal gland adenocarcinoma. A 14.5-year-old spayed female domestic shorthair cat was evaluated for a firm swelling at the left dorsotemporal orbital rim. The orbital mass was excised with preservation of the globe, and adjunctive cryotherapy was performed. A definitive diagnosis of lacrimal gland adenocarcinoma was obtained after histopathologic evaluation and histochemical staining with periodic acid-Schiff and mucicarmine. Thirteen months postoperatively, tumor regrowth occurred with a much larger osteolytic lesion, and a second surgery was performed consisting of tumor excision with implantation of carboplatin-impregnated calcium sulfate hemihydrate beads. The cat has remained free of recurrence 11 months after the second surgery (26 months after initial diagnosis and surgery). A feline orbital lacrimal gland adenocarcinoma was successfully managed utilizing globe-preserving surgical excision with adjunctive cryotherapy and subsequent carboplatin-impregnated bead implantation. Orbital lacrimal gland adenocarcinoma in cats may not be as aggressive as other forms of periocular, head, and neck adenocarcinomas.

Background Endoscopy is performed for direct inspection of the mucosa and acquisition of biopsies in dogs with inflammatory bowel disease (IBD). Aim To evaluate the interobserver agreement in the endoscopic assessment of duodenal mucosa in dogs with IBD. Methods Thirty-five archived endoscopic images of grossly normal (n = 6) and inflamed (n = 29) duodenal mucosa were displayed to 3 expert and 5 trainee endoscopists. Each image was assessed independently by endoscopists for mucosal abnormalities using established indices (of hyperemia, granularity, friability, lymphatic dilatation, and erosions) or interpreted as normal mucosa (trial 1). A repeated trial (trial 2) was performed with the same images presented in random order 1 month later, and accompanied by a visual template. Results There was slight interobserver agreement in initial mucosal assessment for expert and trainee endoscopists in trial 1 (kappa ≤ 0.02, P > .05). Interobserver agreement improved in trial 2 for both expert and trainee endoscopists (kappa = 0.2, P > .05) for experts and (P

Isobutyl-deoxynyboquinone (IB-DNQ) is a selective substrate for NAD(P)H:quinone oxidoreductase (NQO1), an enzyme overexpressed in many solid tumors. Following activation by NQO1, IB-DNQ participates in a catalytic futile reduction/reoxidation cycle with consequent toxic reactive oxygen species generation within the tumor microenvironment. To elucidate the potential of IB-DNQ to serve as a novel anticancer agent, in vitro studies coupled with in vivo pharmacokinetic and toxicologic investigations in the domestic felid species were conducted to investigate the tractability of IB-DNQ as a translationally applicable anticancer agent. First, using feline oral squamous cell carcinoma (OSCC) as a comparative cancer model, expressions of NQO1 were characterized in not only human, but also feline OSCC tissue microarrays. Second, IB-DNQ mediated cytotoxicity in three immortalized feline OSCC cell lines were studied under dose-dependent and sequential exposure conditions. Third, the feasibility of administering IB-DNQ at doses predicted to achieve cytotoxic plasma concentrations and biologically relevant durations of exposure were investigated through pharmacokinetic and tolerability studies in healthy research felines. Intravenous administration of IB-DNQ at 1.0–2.0 mg/kg achieved peak plasma concentrations and durations of exposure reaching or exceeding predicted in vitro cytotoxic concentrations. Clinical adverse side effects including ptyalism and tachypnea exhibited during and post-IV infusion of IB-DNQ were transient and tolerable. Additionally, IB-DNQ administration did not produce acute or delayed-onset unacceptable hematologic, non-hematologic, or off-target oxidative toxicities. Collectively, the findings reported here within provide important safety and pharmacokinetic data to support the continued development of IB-DNQ as a novel anticancer strategy for NQO1 expressing cancers.