ObjectivesThe aims of the study were to describe a technique for feline ala vestibuloplasty and report long-term postoperative outcomes in 27 brachycephalic (BC) cats.MethodsThe study was a retrospective, questionnaire-based study of owned, clinically affected BC cats (n = 27). Owners completed a single, two-part questionnaire regarding presence or absence, frequency or severity of clinical signs before and more than 6 months after ala vestibuloplasty. The questionnaire consisted of questions regarding respiratory and gastrointestinal signs, sleep and activity-related behaviors, and ocular, aural and dental health before and after surgery. Response options were scored and individual scores summed to give a total clinical severity score for each cat (range 0-129). Relationships between clinical variables and outcome were evaluated by regression analysis. A total of 13 cats in the cohort were also enrolled in a previous questionnaire-based study reporting real-time preoperative clinical signs. Owner responses regarding preoperative clinical signs gathered at that time and in the present study were compared to assess for recall bias.ResultsOf the 27 cats, 25 (92.5%) sustained long-term clinical improvement for a mean of 1190 days (range 354-1802 days) after ala vestibuloplasty. Median clinical severity score improved from 48 preoperatively to 17 postoperatively (P <0.0001). Owners reported reduced frequencies of sneezing (P <0.0001), coughing (P = 0.001), nasal discharge (P = 0.0002), snoring (P <0.0001), open-mouth breathing (P = 0.001), dyspnea (P = 0.0001), difficulty eating (P = 0.04), messy eating (P = 0.01), dyspnea while eating (P = 0.003), regurgitation (P = 0.03), vomiting (P = 0.03) and dyspnea during activity (P = 0.007). Owners also reported increased frequency (P = 0.0002) and duration (P = 0.0004) of activity. Owners of cats enrolled in both studies recalled their cats' preoperative clinical signs as slightly more severe than originally reported.Conclusions and relevanceAla vestibuloplasty yields long-term clinical improvements in cats' respiratory, gastrointestinal, sleep, activity, aural and ocular signs. Ala vestibuloplasty should be considered for effective treatment of the described clinical signs of feline BC syndrome.

Hepatocellular carcinoma (HCC) is an aggressive disease with poor response to current therapies, highlighting the need for more effective therapeutic strategies. Preclinical HCC models are necessary tools for assessment of novel therapies. Pigs offer a valuable disease model due to their similarities with humans and their large size which allows testing clinically relevant procedures. Here, we aimed to develop HCC cell and animal models by precise gene manipulation of primary porcine hepatocytes. Hepatocytes were isolated from minipigs (n=4) and subjected to CRISPR knockout (KO) of tumor suppressor genes, with or without oncogene overexpression (OE). Gene alteration combinations included KO of TP53, PTEN, and/or CDKN2A, with or without c-myc overexpression. Gene alterations were validated by Sanger sequencing, PCR, and Western blotting. The developed cell lines were injected subcutaneously into severe combined immunodeficient (SCID) mice to confirm their tumorigenicity and assess histological features. Cells with TP53KO; PTENKO; CDKN2AKO; c-mycOE (TPKM) were then autologously injected into pigs (n=2) by percutaneous ultrasound-guided liver parenchymal injection and tumor development was monitored by ultrasound and CT imaging. Tumors from mice and pigs were analyzed by histological and transcriptional analyses. The induced gene alterations in porcine hepatocytes resulted in the successful development and propagation of four distinct cell lines, all validated for the intended modifications. Injection of these cells into SCID mice resulted in tumor development confirming in vivo tumorigenicity. Histological analysis of mouse xenograft tumors identified epithelial neoplasms with multiphenotypic cells, displaying moderate to poor differentiation, and closely mimicking human liver cancer. In pigs, autologous injection of TPKM cells resulted in intrahepatic mass formation within 3 weeks. Histological analysis of the porcine masses revealed neoplastic cells with positive Arginase staining, negative CK19 staining, and intratumoral immune cell infiltration. Transcriptional analysis of the mouse and pig tumors showed activation of pathways associated with cancer cell proliferation and hepatic fibrosis. This study successfully establishes genetically defined HCC models with histological and molecular features resembling human HCC by CRISPR editing of primary porcine hepatocytes. These innovative HCC cell models provide valuable tools for drug screening and mechanistic studies, and the porcine model is a promising tool that harbors defined tumor driver mutations and is suitable for locoregional therapy testing. Together, these novel HCC cell and animal models offer promising avenues for preclinical evaluation of innovative therapeutic strategies. Lobna Elkhadragy, Olayinka G. David, Caitlyn C. Castillo, Isadora Andre Rosa Lopes1, Hannah Liu, Luke R. Jordan, Luke N. Redlon, Grace Guzman, Jonathan P. Samuelson, Lawrence B. Schook, Amaia Lujambio, Kyle M. Schachtschneider, Ron C. Gaba. Modeling HCC molecular and histological features by CRISPR editing of primary hepatocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6497.

Hepatocellular carcinoma (HCC) is an aggressive disease with poor prognosis, necessitating preclinical models for evaluating novel therapies. Large-animal models are particularly valuable for assessing locoregional therapies, which are widely employed across HCC stages. This study aimed to develop a large-animal HCC model with tailored tumor mutations. The Oncopig, a genetically engineered pig with inducible TP53R167H and KRASG12D, was used in the study. Hepatocytes were isolated from Oncopigs and exposed to Cre recombinase in vitro to create HCC cells, and additional mutations were introduced by CRISPR/Cas9 knockout of PTEN and CDKN2A. These edits increased Oncopig HCC cell proliferation and migration. Autologous HCC cells with these CRISPR edits were implanted into Oncopigs using two approaches: ultrasound-guided percutaneous liver injections, which resulted in the development of localized intrahepatic masses, and portal vein injections, which led to multifocal tumors that regressed over time. Tumors developed by both approaches harbored PTEN and CDKN2A knockout mutations. This study demonstrates the feasibility of developing genetically tailored HCC tumors in Oncopigs using somatic cell CRISPR editing and autologous implantation, providing a valuable large-animal model for in vivo therapeutic assessment.

Between September and November 2021, 5 snow leopards (Panthera uncia) and 1 lion (Panthera leo) were naturally infected with severe acute respiratory coronavirus 2 (SARS-CoV-2) and developed progressive respiratory disease that resulted in death. Severe acute respiratory syndrome coronavirus 2 sequencing identified the delta variant in all cases sequenced, which was the predominant human variant at that time. The time between initial clinical signs and death ranged from 3 to 45 days. Gross lesions in all 6 cats included nasal turbinate hyperemia with purulent discharge and marked pulmonary edema. Ulcerative tracheitis and bronchitis were noted in 4 cases. Histologically, there was necrotizing and ulcerative rhinotracheitis and bronchitis with fibrinocellular exudates and fibrinosuppurative to pyogranulomatous bronchopneumonia. The 4 cats that survived longer than 8 days had fungal abscesses. Concurrent bacteria were noted in 4 cases, including those with more acute disease courses. Severe acute respiratory syndrome coronavirus 2 was detected by in situ hybridization using probes against SARS-CoV-2 spike and nucleocapsid genes and by immunohistochemistry. Viral nucleic acid and protein were variably localized to mucosal and glandular epithelial cells, pneumocytes, macrophages, and fibrinocellular debris. Based on established criteria, SARS-CoV-2 was considered a contributing cause of death in all 6 cats. While mild clinical infections are more common, these findings suggest that some SARS-CoV-2 variants may cause more severe disease and that snow leopards may be more severely affected than other felids.

Soft tissue sarcoma subtype classifications

OBJECTIVE:To describe the presentation, management, and postmortem examination findings in a dog with confirmed lisdexamfetamine dimesylate (LDX) toxicosis.CASE SUMMARY:A 3-year-old female neutered mixed breed dog initially presented with neurological signs suspected to be secondary to LDX toxicosis. The dog was treated as typical for amphetamine toxicoses but developed severe respiratory and cardiovascular signs throughout their hospitalization. The progression of the cardiopulmonary signs led to cardiopulmonary arrest, for which CPR was unsuccessful. Postmortem examination exhibited severe hemorrhage throughout multiple organ systems. Toxicology testing confirmed the presence of unaltered LDX and its metabolite, amphetamine.NEW OR UNIQUE INFORMATION PROVIDED:This is the first case report documenting a severe progression of clinical signs and postmortem examination findings in a case of confirmed LDX toxicosis in a dog. Although the patient did not survive treatment, postmortem examination and microscopic evaluation of tissues allowed visualization of the extent of systemic pathophysiology. With prompt treatment, the prognosis of amphetamine toxicosis in dogs is generally considered good; however, this case report demonstrates a severe case in which even prompt and appropriate treatment did not prevent mortality. This suggests a need to establish negative prognostic indicators for which to monitor in cases of amphetamine toxicosis. Finally, this report is also unique in the fact that the LDX toxicosis was confirmed using a toxicological analysis technique not previously described clinically in dogs.

Testicular germ cell tumors (TGCTs) can be treated with cisplatin-based therapy. However, a clinically significant number of cisplatin-resistant patients die from progressive disease as no effective alternatives exist. Curative cisplatin therapy results in acute and life-long toxicities in the young TGCT patient population providing a rationale to decrease cisplatin exposure. In contrast to genetic alterations, recent evidence suggests that epigenetics is a major driving factor for TGCT formation, progression, and response to chemotherapy. Hence, targeting epigenetic pathways with “epidrugs” is one potential relatively unexplored strategy to advance TGCT treatment beyond cisplatin. In this report, we demonstrate for the first time that targeting polycomb demethylases KDM6A and KDM6B with epidrug GSK-J4 can treat both cisplatin-sensitive and -resistant TGCTs. While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin. We validated KDM6A/KDM6B as the target of GSK-J4 since KDM6A/KDM6B genetic depletion had a similar effect to GSK-J4 on cisplatin-mediated anti-tumor activity and transcriptome alterations. Pharmacologic and genetic targeting of KDM6A/KDM6B potentiated or primed the p53-dominant transcriptional response to cisplatin, with also evidence for basal activation of p53. Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.

Background The successful clinical translation of novel immunotherapies begins with evaluation in animal models that accurately recapitulate the complex tumor-immune interactions observed in human cancers. Naturally-occurring tumors in pet dogs present an under-utilized opportunity to assess the safety and efficacy of investigational immunotherapies, with particular advantages over mouse models including patient characteristics (e.g. immune senescence, weight, age), tumor heterogeneity (e.g. mutational burden, metastasis, immune infiltration), and dosing considerations (e.g. biodistribution, metabolic rate). Here, we examine the anti-tumor responses driven by engineered IL-2 and IL-12 cytokines in canine soft tissue sarcomas and oral melanomas. Methods We have previously reported on our strategy to recombinantly express IL-2 and IL-12 cytokines as fusion proteins to a collagen-binding protein domain and albumin, which enable anchoring within the tumor microenvironment following intratumoral administration.1 Given the promising activity and tolerability observed in syngeneic murine tumor models, we canine-ized these cytokine fusion proteins for evaluation in canine cancers. Pet dogs with soft tissue sarcoma were enrolled for treatment and received cytokines at different intervals prior to surgical tumor excision. Tumor tissue was then profiled by immunohistochemistry and Nanostring for cytokine-driven changes to the tumor microenvironment. Pet dogs with advanced oral melanoma were enrolled in a dose-escalation trial, receiving a single 9 Gy dose of radiation, followed by intratumoral cytokines every two weeks for 6 total doses. Serum was collected for analysis of systemic cytokine/chemokine response, with serial blood count/chemistry profiles and CT scans taken for the assessment of safety and radiologic response, respectively. Results Intratumoral dosing of collagen-binding cytokines was well tolerated by tumor-bearing dogs at the lowest 3 investigational doses, with manageable cytokine release syndrome observed at the highest tested dose (57 µg/kg IL-2; 6.8 µg/kg IL-12). Transient elevation of systemic IFN-γ and IL-10 was observed following treatment in both tumor types. Analysis of treated sarcoma tissue revealed enhanced infiltration by T-cells, corroborated by increases in gene expression programs associated with cytotoxic immune function.2 Robust anti-tumor responses were observed in melanoma patients, including 6/13 PR and 3/13 CR by RECIST criteria. Two dogs have remained tumor-free nearly 2 years after completing treatment. Conclusions This data supports the safety and activity of collagen-anchored IL-2 and IL-12 after intratumoral delivery in tumor-bearing dogs, combining with standard-of-care radiation therapy or resection. This work highlights the utility of comparative oncologic evaluation in canine tumors alongside murine models to accelerate the build-test-learn design cycle for novel immunotherapies and/or treatment combinations. Acknowledgements We gratefully thank all owners of tumor-bearing dogs for their consent and willingness to participate in this investigational trial. We also thank the Koch Institute Swanson Biotechnology Center for technical support, specifically the histology and integrated genomics and bioinformatics core facilities, supported in part by NCI Grant P30-CA14051. This work was directly supported by NCI Grant R01-CA271243. We also thank William Hwang and Jennifer Su for their technical assistance with the Nanostring nCounter system. References Momin N, et al. Anchoring of intratumorally administered cytokines to collagen safely potentiates systemic cancer immunotherapy. Sci Trans Med. 2019;11:eaaw2614. Stinson JA, Sheen A, et al. Collagen-anchored interleukin-2 and interleukin-12 safely reprogram the tumor microenvironment in canine soft-tissue sarcomas. Clin Cancer Res. 2023;29:2110–22. Ethics Approval All mouse studies were conducted under approval of the MIT Committee on Animal Care in accordance with federal, state, and local guidelines. The study protocol for the treatment of oral melanoma and soft tissue sarcomas in pet dogs was reviewed and approved by the Institutional Animal Care and Use Committee of the University of Illinois at Urbana-Champaign. All pet dog owners provided written consent before enrollment in the trial.

AbstractPurpose:Cytokine therapies such as IL2 and IL12 suffer from impractically small therapeutic windows driven by their on-target, off-tumor activity, limiting their clinical potential despite potent antitumor effects. We previously engineered cytokines that bind and anchor to tumor collagen following intratumoral injection, and sought to test their safety and biomarker activity in spontaneous canine soft-tissue sarcomas (STS).Experimental Design:Collagen-binding cytokines were canine-ized to minimize immunogenicity and were used in a rapid dose-escalation study in healthy beagles to identify a maximum tolerated dose. Ten client-owned pet dogs with STS were then enrolled into trial, receiving cytokines at different intervals prior to surgical tumor excision. Tumor tissue was analyzed through IHC and NanoString RNA profiling for dynamic changes within treated tumors. Archived, untreated STS samples were analyzed in parallel as controls.Results:Intratumorally administered collagen-binding IL2 and IL12 were well tolerated by STS-bearing dogs, with only Grade 1/2 adverse events observed (mild fever, thrombocytopenia, neutropenia). IHC revealed enhanced T-cell infiltrates, corroborated by an enhancement in gene expression associated with cytotoxic immune function. We found concordant increases in expression of counter-regulatory genes that we hypothesize would contribute to a transient antitumor effect, and confirmed in mouse models that combination therapy to inhibit this counter-regulation can improve responses to cytokine therapy.Conclusions:These results support the safety and activity of intratumorally delivered, collagen-anchoring cytokines for inflammatory polarization of the canine STS tumor microenvironment. We are further evaluating the efficacy of this approach in additional canine cancers, including oral malignant melanoma.

Purpose: To investigate the pharmacokinetics (PK) and early effects of conventional transarterial chemoembolization (TACE) using sorafenib and doxorubicin on tumor necrosis, hypoxia markers, and angiogenesis in a rabbit VX2 liver tumor model. Materials and Methods: VX2 tumor-laden New Zealand White rabbits (N = 16) were divided into 2 groups: 1 group was treated with hepatic arterial administration of ethiodized oil and doxorubicin emulsion (DOX-TACE), and the other group was treated with ethiodized oil, sorafenib, and doxorubicin emulsion (SORA-DOX-TACE). Animals were killed within 3 days of the procedure. Levels of sorafenib and doxorubicin were measured in blood, tumor, and adjacent liver using mass spectrometry. Tumor necrosis was determined by histopathological examination. Intratumoral hypoxia-inducible factor (HIF) 1 alpha, vascular endothelial growth factor (VEGF), and microvessel density (MVD) were determined by immunohistochemistry. Results: The median intratumoral concentration of sorafenib in the SORA-DOX-TACE group was 17.7 mu g/mL (interquartile range [IQR], 7.42-33.5 mu g/mL), and its maximal plasma concentration (C-max) was 0.164 mu g/mL (IQR, 0.0798-0.528 mu g/mL). The intratumoral concentration and C-max of doxorubicin were similar between the groups: 4.08 mu g/mL (IQR, 3.18-4.79 mu g/mL) and 0.677 mu g/mL (IQR, 0.315-1.23 mu g/mL), respectively, in the DOX-TACE group and 1.68 mu g/mL (IQR, 0.795-4.08 mu g/mL) and 0.298 mu g/mL (IQR, 0.241-0.64 mu g/mL), respectively, in the SORA-DOX-TACE group. HIF-1 alpha expression was increased in the SORA-DOX-TACE group than in the DOX-TACE group. Tumor volume, tumor necrosis, VEGF expression, and MVD were similar between the 2 groups. Conclusions: The addition of sorafenib to DOX-TACE delivered to VX2 liver tumors resulted in high intratumoral and low systemic concentrations of sorafenib without altering the PK of doxorubicin.

The purpose of this study was to compare intra-tumoral drug delivery, pharmacokinetics, and treatment response after doxorubicin (DOX) conventional (c-) versus drug-eluting embolic (DEE-) transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor model. Twenty-four rabbits with solitary liver tumors underwent c-TACE (n = 12) (1:2 water-in-oil emulsion, 0.6 mL volume, 2 mg DOX) or DEE-TACE (n = 12) (130,000 70–150 µm 2 mg DOX-loaded microspheres). Systemic, intra-tumoral, and liver DOX levels were measured using mass spectrometry up to 7-day post-procedure. Intra-tumoral DOX distribution was quantified using fluorescence imaging. Percent tumor necrosis was quantified by a pathologist blinded to treatment group. Lobar TACE was successfully performed in all cases. Peak concentration (CMAX, µg/mL) for plasma, tumor tissue, and liver were 0.666, 4.232, and 0.270 for c-TACE versus 0.103, 8.988, and 0.610 for DEE-TACE. Area under the concentration versus time curve (AUC, µg/mL ∗ min) for plasma, tumor tissue, and liver were 18.3, 27,078.8, and 1339.1 for c-TACE versus 16.4, 26,204.8, and 1969.6 for DEE-TACE. A single dose of intra-tumoral DOX maintained cytotoxic levels through 7-day post-procedure for both TACE varieties, with a half-life of 1.8 (c-TACE) and 0.8 (DEE-TACE) days. Tumor-to-normal liver DOX ratio was high (c-TACE, 20.2; DEE-TACE, 13.3). c-TACE achieved significantly higher DOX coverage of tumor vs. DEE-TACE (10.8% vs. 2.3%; P = 0.003). Percent tumor necrosis was similar (39% vs. 37%; P = 0.806). In conclusion, in a rabbit VX2 liver tumor model, both c-TACE and DEE-TACE achieved tumoricidal intra-tumoral DOX levels and high tumor-to-normal liver drug ratios, though c-TACE resulted in significantly greater tumor coverage.

Two aborted Chester White pig fetuses were presented to a veterinary diagnostic laboratory in Illinois. Postmortem examination identified no gross abnormalities. Histologic evaluation revealed multifocal necrosis of chorionic epithelial cells, coalescing areas of mineralization in the placenta, and focal accumulations of viable and degenerate neutrophils in the lung. Intra- and extracellular acid-fast bacilli were identified in the lesions in both the placenta and lungs. Bacterial culture of stomach contents yielded heavy growth of Mycobacterium fortuitum, a rapidly growing nontuberculous mycobacterium (NTM), which was further confirmed through whole-genome sequencing. NTM are opportunistic pathogens commonly found in the soil and in contaminated water supplies. In animals, M. fortuitum is typically introduced through cutaneous wounds leading to infections limited to the skin, with systemic infection being uncommon. To our knowledge, abortion caused by M. fortuitum has not been reported previously.

BACKGROUND:In male dogs, uroepithelial cancers include invasive urothelial carcinoma (iUC) and prostate carcinoma (PCA). The inability to distinguish iUC involving the prostate from PCA results in indiscriminate clinical management strategies that could be suboptimal as first-line chemotherapy for iUC (cisplatin) and PCA (docetaxel) differ in people. Prostate specific membrane antigen (PSMA) is a transmembrane protein, and its overexpression has been identified in human prostate carcinoma and neovasculature associated with solid tumor growth. This study investigates whether differential PSMA expression exists between presumptive canine iUC and PCA among cell lines and archived patient samples, which might allow for improved accuracy in disease-based stratification and optimal chemotherapy selection. Additionally, in vitro sensitivities of reported canine iUC and PCA cell lines to uroepithelial directed chemotherapeutic agents were characterized. RESULTS:Normalized PSMA gene and protein expressions were not significantly different between 5 iUC and 4 PCA cell lines. PSMA protein expression was uniformly observed in uroepithelial cancers regardless of anatomic origin from archived patient samples, further confirming that PSMA cannot differentiate iUC from PCA. In vitro sensitivity of cell lines to uroepithelial directed chemotherapeutics revealed that vinblastine exerted the broadest cytotoxic activity. CONCLUSIONS:Differential expression of PSMA was not identified between canine iUC and PCA cell lines or archived patient samples, and PSMA alone cannot be used for disease stratification. Nonetheless given its conserved overexpression, PSMA may be a targetable surface marker for both canine iUC and PCA. Lastly, in uroepithelial carcinomas, vinblastine might exert the broadest anticancer activity regardless of cellular origin.

Veterinary Clinical PathologyVolume 50, Issue 4 p. 606-610 WHAT IS YOUR DIAGNOSIS? What is your diagnosis? Blood smear review from a cotton-top tamarin Stephen F. Crane, Corresponding Author Stephen F. Crane sfcrane2@illinois.edu orcid.org/0000-0002-9024-3414 Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Correspondence Stephen F. Crane, Department of Pathobiology, College of Veterinary Medicine, University of Illinois. 1008 W Hazelwood Drive, Urbana, IL 61802, USA. Email: sfcrane2@illinois.eduSearch for more papers by this authorAndrea E. Pohly, Andrea E. Pohly Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorMatthew C. Allender, Matthew C. Allender Wildlife Epidemiology Laboratory, Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorJonathan P. Samuelson, Jonathan P. Samuelson Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Veterinary Diagnostic Laboratory, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorMichael F. Rosser, Michael F. Rosser Veterinary Diagnostic Laboratory, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this author Stephen F. Crane, Corresponding Author Stephen F. Crane sfcrane2@illinois.edu orcid.org/0000-0002-9024-3414 Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Correspondence Stephen F. Crane, Department of Pathobiology, College of Veterinary Medicine, University of Illinois. 1008 W Hazelwood Drive, Urbana, IL 61802, USA. Email: sfcrane2@illinois.eduSearch for more papers by this authorAndrea E. Pohly, Andrea E. Pohly Department of Pathobiology, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorMatthew C. Allender, Matthew C. Allender Wildlife Epidemiology Laboratory, Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorJonathan P. Samuelson, Jonathan P. Samuelson Department of Veterinary Clinical Medicine, University of Illinois College of Veterinary Medicine, Urbana, IL, USA Veterinary Diagnostic Laboratory, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this authorMichael F. Rosser, Michael F. Rosser Veterinary Diagnostic Laboratory, University of Illinois College of Veterinary Medicine, Urbana, IL, USASearch for more papers by this author First published: 30 July 2021 https://doi.org/10.1111/vcp.12938Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Volume50, Issue4December 2021Pages 606-610 RelatedInformation

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.

The invasive, locally aggressive nature of feline injection-site sarcomas (FISSs) poses a unique challenge for surgeons to obtain complete margins with surgical excision. Optical coherence tomography (OCT), an imaging technology that uses light waves to generate real-time views of tissue architecture, provides an emerging solution to this dilemma by allowing fast, high-resolution scanning of surgical margins. The purpose of this study was to use OCT to assess surgical margins of FISS and to evaluate the diagnostic accuracy of OCT for detecting residual cancer using six evaluators of varying experience. Five FISSs were imaged with OCT to create a training set of OCT images that were compared with histopathology. Next, 25 FISSs were imaged with OCT prior to histopathology. Six evaluators of varying experience participated in a training session on OCT imaging after which each of the evaluators was given a dataset that included OCT images and videos to score on a scale from cancerous to non-cancerous. Diagnostic accuracy statistics were calculated. The overall sensitivity and specificity for classification of OCT images by evaluators were 78.9% and 77.6%, respectively. Correct classification rate of OCT images was associated with experience, while individual sensitivities and specificities had more variation between experience groups. This study demonstrates the ability of evaluators to correctly classify OCT images with overall low levels of experience and training and also illustrates areas where increased training can improve accuracy of evaluators in interpretation of OCT surgical margin images.

Canine Distemper Virus (CDV) is a multi-host morbillivirus that infects virtually all Carnivora and a few non-human primates. Here we describe a CDV outbreak in an exotic felid rescue center that led to the death of eight felids in the genus Panthera. Similar to domestic dogs and in contrast to previously described CDV cases in Panthera, severe pneumonia was the primary lesion and no viral antigens or CDV-like lesions were detected in the central nervous system. Four tigers succumbed to opportunistic infections. Viral hemagglutinin (H)-gene sequence was up to 99% similar to strains circulating contemporaneously in regional wildlife. CDV lesions in raccoons and skunk were primarily encephalitis. A few affected felids had at least one previous vaccination for CDV, while most felids at the center were vaccinated during the outbreak. Panthera sharing a fence or enclosure with infected conspecifics had significantly higher chances of getting sick or dying, suggesting tiger-tiger spread was more likely than recurrent spillover. Prior vaccination was incomplete and likely not protective. This outbreak highlights the need for further understanding of CDV epidemiology for species conservation and public health.

Histopathologic surgical margin assessment in veterinary patients is an imprecise science with assessment limited to a small proportion of the surgical margin due to time and finances. Incomplete excision of canine mast cell tumours (MCTs) alters treatment recommendations and prognosis. Optical coherence tomography (OCT) is a novel imaging modality that has been reported in a single veterinary study for surgical margin assessment. Twenty-five dogs with 34 MCTs were enrolled in a prospective pilot-study to assess the imaging characteristics of canine MCTs with OCT and to evaluate the feasibility and utility of OCT-guided histopathology. All dogs underwent routine surgical excision of MCTs. OCT imaging was used to assess the entire surgical margin prior to placement in formalin. Either normal areas or areas suspected of incomplete MCT excision were inked. Standard histopathologic sectioning and tangential sectioning of inked areas were performed and compared to OCT results. OCT identified MCT near the surgical margin in 10 of 26 specimens (38.4%). Four specimens suspicious for incomplete margins on OCT had incomplete MCT excision that was missed on standard histopathologic sectioning. Six specimens had OCT-guided sections taken as suspicious, which did not show MCT on histopathology. OCT-guided pathology sections were able to detect incompletely excised MCT near the surgical margin with a sensitivity of 90% and specificity of 56.2% in this preliminary study. OCT imaging shows promise for guiding pathologists to areas of interest to improve the diagnostic accuracy of surgical margin assessment in excised canine MCTs.