@article{benedict_suter_meritet_2024, title={Postmortem pathologic findings in dogs that underwent total body irradiation and hematopoietic cell transplant: A case series of five dogs with B-cell multicentric lymphoma}, ISSN={["1544-2217"]}, DOI={10.1177/03009858241249114}, abstractNote={Alternative therapies that can help achieve complete remission in dogs with lymphoma include total body irradiation and hematopoietic cell transplant, though there are few reports describing successes and pathologic sequelae of these procedures. During a 10-year period, 94 dogs with multicentric lymphoma received a hematopoietic cell transplant following total body irradiation at North Carolina State University College of Veterinary Medicine. Seven of these 94 dogs (7%) died prior to discharge, five (5%) of which presented for postmortem examination. Of these dogs, four received an autologous hematopoietic cell transplant, while one received a haploidentical allogeneic hematopoietic cell transplant. All five dogs had bone marrow depletion with all hematopoietic lines affected. Three had systemic candidiasis, while two had bacterial infections. To the authors' knowledge, this is the first report to document pathologic findings and development of systemic mycoses in dogs post total-body irradiation therapy and hematopoietic cell transplant.}, journal={VETERINARY PATHOLOGY}, author={Benedict, William and Suter, Steven and Meritet, Danielle}, year={2024}, month={May} }
 @article{gareau_sekiguchi_warry_ripoll_sullivan_westfall_chretin_fulton_harkey_storb_et al._2022, title={Allogeneic peripheral blood haematopoietic stem cell transplantation for the treatment of dogs with high-grade B-cell lymphoma}, ISSN={["1476-5829"]}, DOI={10.1111/vco.12847}, abstractNote={AbstractAutologous peripheral blood haematopoietic stem cell transplantation (HCT) cures 33%–40% of dogs with high‐grade B‐cell lymphoma. We hypothesized, based on human allogeneic bone marrow transplantation literature, that transplanting dogs using canine donor leukocyte‐matched CD34+ cells would lead to fewer relapses and increased cure rates. We retrospectively reviewed medical records of dogs diagnosed with high‐grade B‐cell lymphoma who received an identical allogeneic HCT. A total of 15 dogs transplanted at four facilities were identified. Five of fifteen dogs relapsed before transplant. The mean number of donor CD34+ cells/kg harvested and infused into recipient dogs was 8.0 × 106/kg (range: 2.08 × 106/kg–2.9 × 107/kg). The median disease‐free interval and overall survival of all dogs was 1095 days (range: 9–2920 days) and 1115 days (range: 9–2920 days), respectively. Two of five dogs, not in remission at transplant, died in the hospital. The median disease‐free interval and overall survival of the remaining three dogs was 25 days (range: 15–250 days) and 1100 days (range: 66–1902 days), respectively. The median disease‐free interval and overall survival of the 10 dogs who had not relapsed was 1235 days (range: 19–2920 days) and 1235 days (range: 19–2920 days), respectively. One dog died soon after discharge of presumed gastric‐dilatation‐volvulus. Eight of nine remaining dogs lived >4 yrs post‐alloHCT, leading to a cure rate of 89%. Acute graft versus host disease was seen in three dogs. These results suggest that allogeneic HCT can cure ~50% more dogs than those treated with autologous HCT.}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Gareau, Alexandra and Sekiguchi, Toko and Warry, Emma and Ripoll, Alexandra Z. and Sullivan, Edmund and Westfall, Theresa and Chretin, John and Fulton, Lisa M. and Harkey, Michael and Storb, Rainer and et al.}, year={2022}, month={Jul} }
 @article{culler_vigani_ripoll_gareau_suter_2022, title={Centrifugal therapeutic plasma exchange in dogs with immune-mediated hemolytic anemia (2016-2018): 7 cases}, ISSN={["1476-4431"]}, DOI={10.1111/vec.13196}, abstractNote={AbstractObjectiveTo describe the technique of centrifugal therapeutic plasma exchange (cTPE) in dogs diagnosed with immune‐mediated hemolytic anemia (IMHA) and summarize the outcome of the procedure.DesignRetrospective review of cTPE performed at North Carolina State University from 2016 to 2018, through a search of the institutional database for cTPE and IMHA.SettingUniversity teaching hospital.AnimalsSeven dogs with confirmed IMHA were presented to a university teaching hospital ICU for cTPE. Six dogs were not responsive to standard medical management with immunosuppressive agents, while 1 dog presented before immunosuppressive agents were begun.InterventionsAll dogs underwent multiple cTPE procedures using 1 of 2 commercially available apheresis systems.Measurements and Main ResultsAt presentation, the median HCT was 0.15 L/L (15.7%) (range, 0.10–0.19 L/L [10.3%–19%]) and the median total serum bilirubin was 32.5 mmol/L (1.9 mg/dl) (range, 15.4–597 mmol/L [0.9–34.9 mg/dl]). The median number of transfusions before cTPE was 1 (range, 1–4), with a median total of infused RBCs of 12.9 ml/kg (range, 8.8–37 ml/kg). cTPE with an exchange of ≥4 times total plasma volumes was used to decrease the level of circulating autoreactive antibodies. The median total plasma volumes exchanged was 4.5 times (range, 2.5–6.5 times) over 2–4 procedures. Anticoagulation was performed using a combination of systemic heparinization and regional citrate in all dogs. Six of 7 dogs (85.7%) were discharged from the hospital and were alive 90 days after discharge. One dog (14%) did not respond to cTPE (∼6.5 times total plasma volume exchanged) and was euthanized.ConclusionscTPE is a feasible and relatively safe bridging treatment option for the management of canine IMHA.}, journal={JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE}, author={Culler, Christine A. and Vigani, Alessio and Ripoll, Alexandra Z. and Gareau, Alexandra and Suter, Steven E.}, year={2022}, month={May} }
 @article{doka_suter_mastromauro_bennett_hess_2022, title={Doxorubicin for treatment of histiocytic sarcoma in dogs: 31 cases (2003-2017)}, volume={260}, ISSN={["1943-569X"]}, DOI={10.2460/javma.21.11.0498}, abstractNote={Abstract

OBJECTIVE
To evaluate the efficacy of doxorubicin for treatment of histiocytic sarcoma (HS) in dogs, whether administered as the sole treatment or as an adjunct to surgery or radiation therapy.


ANIMALS
31 client-owned dogs with localized or disseminated HS examined between 2003 and 2017.


PROCEDURES
Medical records were reviewed retrospectively, and data were collected. The Kaplan-Meier method was used to estimate time-to-progression from the date of first doxorubicin administration and survival time from initial diagnosis. Factors that could be associated with poorer outcomes with doxorubicin treatment were analyzed with log-rank tests.


RESULTS
The objective response rate (ORR) was 26%. When stratified by disease status, dogs with localized and disseminated forms experienced 43% and 21% ORRs, respectively. Median time to progression after initiating doxorubicin treatment (n = 30 dogs) was 42 days. Median survival time from initial diagnosis to death (n = 29 dogs) was 169 days. Complete responses were obtained in only 2 dogs that had localized disease and received multimodality therapy.


CLINICAL RELEVANCE
Benefits of doxorubicin administration in canine HS are modest, with a limited ORR and delay in tumor progression, and are comparable to effects attained with other single-agent regimens.
}, number={14}, journal={JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION}, author={Doka, Rhiannon M. and Suter, Steven E. and Mastromauro, Michael L. and Bennett, Ashley L. and Hess, Paul R.}, year={2022}, month={Nov}, pages={1827–1833} }
 @article{chalifoux_butty_mauro_moyle_ehrhardt_robertson_labato_culler_londono_vigani_et al._2022, title={Outcomes of 434 dogs with non-steroidal anti-inflammatory drug toxicosis treated with fluid therapy, lipid emulsion, or therapeutic plasma exchange}, volume={12}, ISSN={["1939-1676"]}, url={http://dx.doi.org/10.1111/jvim.16603}, DOI={10.1111/jvim.16603}, abstractNote={AbstractBackgroundTraditional management of non‐steroidal anti‐inflammatory drug (NSAID) intoxication includes gastrointestinal decontamination, intravenous administration of fluids (IVF), and gastroprotection. Intravenous administration of lipid emulsion (ILE) and therapeutic plasma exchange (TPE) are popular novel therapeutic strategies.HypothesisCompare outcomes of dogs treated with IVF, ILE, and TPE for NSAID intoxications and evaluate outcome predictors for drug subgroups.AnimalsFour hundred thirty‐four dogs with NSAID intoxications (2015‐2020).MethodsMulticenter retrospective study of ibuprofen, carprofen, and naproxen intoxication. An ordinal outcome was defined as mild gastrointestinal, moderate kidney, or signs of severe central nervous system disease.ResultsSigns of neurological disease were overrepresented and acute kidney injury underrepresented in the TPE group among dogs exposed to kidney‐ or CNS‐toxic doses (P = .05), though all TPE dogs with signs of neurological disease had evidence of neurotoxicity at presentation. Dogs treated with IVF had a higher maximal creatinine concentration (median, 1.1 mg/dL; range, 0.4‐8.44 mg/dL) compared with IVF + ILE (median, 0.9 mg/dL; range, 0.4‐6.2 mg/dL; P = .01). Increased maximum time to presentation (P < .001), higher baseline creatinine (P < .001) and PCV (P = .007), and absence of induced emesis (P < .001) were associated with greater clinical severity. Ibuprofen toxicosis was associated with more severe clinical signs compared with carprofen (P = .03). Overall survival rate was 99%.Conclusions and Clinical ImportanceNSAID toxicosis generally carries an excellent prognosis in dogs. Despite similar outcomes of lower incidence of AKI in the TPE group, and slightly lower maximal creatinine concentration in dogs treated with ILE vs IVF alone, ILE and TPE should be considered in the management of severe NSAID toxicosis.}, number={1}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, publisher={Wiley}, author={Chalifoux, Nolan V. and Butty, Emmanuelle M. and Mauro, Katie D. and Moyle, Rachel B. and Ehrhardt, Caryn M. and Robertson, James B. and Labato, Mary A. and Culler, Christine A. and Londono, Leonel A. and Vigani, Alessio and et al.}, year={2022}, month={Dec} }
 @article{butty_suter_chalifoux_lynch_mauro_moyle_ehrhardt_robertson_culler_londono_et al._2022, title={Outcomes of nonsteroidal anti-inflammatory drug toxicosis treated with therapeutic plasma exchange in 62 dogs}, volume={8}, ISSN={["1939-1676"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85136301395&partnerID=MN8TOARS}, DOI={10.1111/jvim.16507}, abstractNote={AbstractBackgroundTherapeutic plasma exchange (TPE) is gaining popularity for the management of nonsteroidal anti‐inflammatory drug (NSAID) overdose in dogs.Hypothesis/ObjectivesDescribe a population of dogs treated with TPE for NSAID overdose.AnimalsSixty‐two dogs with NSAID overdose treated with TPE.MethodsMulticenter retrospective study of dogs treated with TPE for ibuprofen, carprofen, or naproxen overdose.ResultsThe median dose of ibuprofen, carprofen or naproxen ingested was 533 mg/kg (range, 36‐4857 mg/kg), 217 mg/kg (range, 88‐625 mg/kg) and 138 mg/kg (range, 26‐3000 mg/kg), respectively. Based on previously established toxic ranges for each NSAID, 2 (3.2%), 14 (22.6%), and 46 (74.2%) dogs ingested a gastrointestinal, renal, and neurological toxic dose, respectively. The median time between ingestion and presentation was 4 hours (range, 1‐20 hours). The median number of plasma volumes processed was 1.6 (range, 0.4‐2.2). The median TPE session duration was 2 hours (range, 1‐4.5 hours). Circuit clotting developed during 8 (12.9%) sessions. Patient adverse events reported during 21 (33.8%) sessions consisted of urticaria (12.9%), asymptomatic hypocalcemia (9.6%), and hypotension (9.6%). The median duration of hospitalization was 2.25 days (range, 1‐11 days). Sixty‐one (98.4%) dogs survived to discharge, and none were rehospitalized. Thirty‐one (91.1%) of the 34 dogs with at least 1 follow‐up visit were not azotemic at the time of reevaluation.Conclusions and Clinical ImportanceThis population of dogs managed with TPE had excellent outcomes, even in cases of high NSAID dose ingestion. When TPE is available and the time frame is appropriate, this extracorporeal modality should be considered for the management of NSAID overdose.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Butty, Emmanuelle M. and Suter, Steven E. and Chalifoux, Nolan V and Lynch, Alex M. and Mauro, Katie D. and Moyle, Rachel B. and Ehrhardt, Caryn M. and Robertson, James B. and Culler, Christine A. and Londono, Leonel A. and et al.}, year={2022}, month={Aug} }
 @article{gareau_ripoll_suter_2021, title={A Retrospective Analysis: Autologous Peripheral Blood Hematopoietic Stem Cell Transplant Combined With Adoptive T-Cell Therapy for the Treatment of High-Grade B-Cell Lymphoma in Ten Dogs}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.787373}, abstractNote={In humans, a type of cellular immunotherapy, called adoptive T cell transfer (ACT), can elicit curative responses against hematological malignancies and melanoma. ACT using ex vivo expanded peripheral blood T-cells after multiagent chemotherapy enhances tumor-free survival of dogs with B-cell lymphoma (LSA). Since 2008, our group has been performing autologous peripheral blood hematopoietic stem cell transplants (autoPBHSCT) for the treatment of canine high-grade B-cell LSA, although relapse of residual disease is a common cause of reduced survival in ~70% of treated dogs. We reasoned that a more aggressive treatment protocol combining CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy, autoPBHSCT, and ACT to treat 10 dogs with B-cell LSA could lead to better outcomes when compared to dogs treated with CHOP chemotherapy and autoPBHSCT alone. Using this protocol, once dogs achieved complete hematologic reconstitution post-autoPBHSCT, CD3+ CD8+ and CD3+CD4+ T-cells were expanded from the peripheral blood at a commercial laboratory. Two to four ACT infusions were given to each dog, with a total of 23 infusions given. Infusions were administered with no complications or adverse events. The median cell dose for all infusions was 5.62 x 106 cells/kg (range: 2.59 x 106-8.55 x 106 cells/kg). 4/10 (40%) of dogs were cured of their disease (defined as disease-free for ≥2 years post-autoPBHSCT). Our results confirm that the autoPBHSCT protocol did not hinder the in vitro expansion of autologous peripheral blood T-cells and that the final product could be administered safely, with no adverse events recorded. Finally, since only ten dogs were treated, our results can only suggest that the administration of ACT to dogs after multiagent chemotherapy and autoPHSCT did not lead to a statistically significant increase in median disease-free interval and overall survival when compared to dogs who received CHOP chemotherapy and autoPHSCT alone.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Gareau, Alexandra and Ripoll, Alexandra Z. and Suter, Steven E.}, year={2021}, month={Dec} }
 @article{leblanc_mazcko_cherukuri_berger_kisseberth_brown_lana_weishaar_flesner_bryan_et al._2021, title={Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs}, volume={27}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.CCR-21-0315}, abstractNote={Abstract
               
                  Purpose:
                  The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression.
               
               
                  Patients and Methods:
                  A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes.
               
               
                  Results:
                  There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144–237] and 282 days (95% CI, 224–383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157–217) and 280 days (95% CI, 252–332), respectively.
               
               
                  Conclusions:
                  In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.
               }, number={11}, journal={CLINICAL CANCER RESEARCH}, author={LeBlanc, Amy K. and Mazcko, Christina N. and Cherukuri, Aswini and Berger, Erika P. and Kisseberth, William C. and Brown, Megan E. and Lana, Susan E. and Weishaar, Kristen and Flesner, Brian K. and Bryan, Jeffrey N. and et al.}, year={2021}, month={Jun}, pages={3005–3016} }
 @article{sekiguchi_vigani_ripoll_taylor_culler_suter_2020, title={Clinical Application of Apheresis in Very Small Dogs Weighing < 8 kg to Pediatric Patients}, volume={24}, ISSN={["1744-9987"]}, DOI={10.1111/1744-9987.13432}, abstractNote={AbstractApheresis in low body weight children and adolescents is challenging due to a variety of technical and clinical issues including vascular access, low total blood volume, and hypotension. Although dogs have been a valuable preclinical model for apheresis, the procedure can be challenging since many pure‐bred dogs are extremely small. Therefore, apheresis in these very small breeds presents very similar challenges as seen when performing the procedure in very low body weight people. We describe apheresis of four very small dogs, weighing from 4.6 to 7.6 kg, using either a COBESpectra and Spectra Optia apheresis system (Terumo BCT, Lakewood, CO, USA). Two dogs underwent large volume leukapheresis to collect mononuclear cells in preparation for hematopoietic stem cell transplantation and two dogs underwent therapeutic plasma exchange to treat an immune‐mediated disease. In all cases, a dual‐lumen hemodialysis catheter placed in the jugular vein provided adequate machine inlet and return flow rates. Machine priming was necessary to maintain hemodynamic stability during the beginning of the procedure, and rinseback was avoided for the same reason. Anticoagulant citrate dextrose solution, solution A was used for the large volume leukapheresis procedures and a combination of anticoagulant citrate dextrose solution, solution A and heparin was used for the therapeutic plasma exchange procedures. As such, serum iCa levels were regularly monitored and 10% calcium gluconate constant rate infusions were used to prevent citrate toxicity. All dogs completed the aphereses with no life‐threatening adverse events. We conclude that aphereses in very small dogs is feasible if close attention is paid to hemodynamic stability and citrate toxicity.}, number={3}, journal={THERAPEUTIC APHERESIS AND DIALYSIS}, author={Sekiguchi, Tomoko and Vigani, Alessio and Ripoll, Alexandra Z. and Taylor, Scott and Culler, Christine and Suter, Steven E.}, year={2020}, month={Jun}, pages={333–342} }
 @article{gieger_nolan_roback_suter_2019, title={Implementation of total body photon irradiation as part of an institutional bone marrow transplant program for the treatment of canine lymphoma and leukemias}, volume={60}, ISSN={["1740-8261"]}, DOI={10.1111/vru.12776}, abstractNote={AbstractA total body irradiation (TBI) protocol was developed to support a bone marrow transplant (BMT) program for the treatment of canine hematologic malignancies. The purpose of this prospective study is to describe implementation of the protocol and resultant dosimetry. Nongraphic manual treatment planning using 6 MV photons, isocentric delivery, 40 × 40 cm field size, wall‐mounted lasers to verify positioning, a lucite beam spoiler (without use of bolus material), a dose rate of 8.75 cGy/min at patient isocenter, and a source‐to‐axis distance of 338 cm were used for TBI. A monitor unit calculation formula was derived using ion chamber measurements and a solid water phantom. Five thermoluminescent dosimeters (TLDs) were used at various anatomic locations in each of four cadaver dogs, to verify fidelity of the monitor unit formula prior to clinical implementation. In vivo dosimetric data were then collected with five TLDs at various anatomic locations in six patients treated with TBI. A total dose of 10 Gy divided into two 5 Gy fractions was delivered approximately 16 h apart, immediately followed by autologous stem cell transplant. The mean difference between prescribed and delivered doses ranged from 99% to 109% for various sites in cadavers, and from 83% to 121% in clinical patients. The mean total body dose in cadavers and clinical patients when whole body dose was estimated by averaging doses measured by variably placed TLDs ranged from 98% to 108% and 93% to 102% of the prescribed dose, respectively, which was considered acceptable. This protocol could be used for institutional implementation of TBI.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Gieger, Tracy L. and Nolan, Michael W. and Roback, Donald M. and Suter, Steven E.}, year={2019}, month={Sep}, pages={586–593} }
 @article{hallman_hauck_williams_hess_suter_2019, title={Incidence and risk factors associated with development of clinical cardiotoxicity in dogs receiving doxorubicin}, volume={33}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/jvim.15414}, DOI={10.1111/jvim.15414}, abstractNote={BackgroundDoxorubicin (DOX) can cause cumulative cardiotoxicity in dogs, but the incidence of clinical cardiotoxicity in dogs receiving DOX has not been determined.Hypothesis/ObjectivesTo determine if the duration of DOX infusion influences the incidence of cardiotoxicity, to characterize the incidence of clinical cardiotoxicity in dogs during or after DOX chemotherapy, and to identify any risk factors associated with cardiotoxicity.AnimalsFour‐hundred ninety‐four dogs that received at least 1 dose of DOX for the treatment of cancer.MethodsRetrospective study of dogs that received DOX from 2006 to 2015.ResultsOf 494 dogs, 20 (4.0%) developed clinical cardiotoxicity. The duration of DOX infusion was not significantly associated with clinical cardiotoxicity, whereas a higher cumulative dose of DOX, higher body weight, decreases in fractional shortening after 5 doses of DOX, and development of ventricular premature contractions were significantly associated with clinical cardiotoxicity. High‐risk breeds for developing dilated cardiomyopathy had an incidence of 15.4%, whereas low‐risk breeds had an incidence of 3.0%.Conclusions and Clinical ImportanceAlthough the duration of DOX infusion did not influence the incidence of cardiotoxicity, premature contractions and decreases in fractional shortening should raise concern for the development of clinical cardiotoxicity. Overall, the incidence of clinical DOX‐induced cardiotoxicity is low, but Boxers and other breeds at high risk for dilated cardiomyopathy may be at an increased risk.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Hallman, Briana E. and Hauck, Marlene L. and Williams, Laurel E. and Hess, Paul R. and Suter, Steven E.}, year={2019}, month={Jan}, pages={783–791} }
 @article{yousefpour_mcdaniel_prasad_ahn_li_subrahmanyan_weitzhandler_suter_chilkoti_2018, title={Genetically Encoding Albumin Binding into Chemotherapeutic-loaded Polypeptide Nanoparticles Enhances Their Antitumor Efficacy}, volume={18}, ISSN={["1530-6992"]}, DOI={10.1021/acs.nanolett.8b03558}, abstractNote={We report the development of drug-encapsulating nanoparticles that bind endogenous albumin upon intravenous injection and evaluate their in vivo performance in a murine as well as canine animal model. The gene encoding a protein-G derived albumin binding domain (ABD) was fused to that of a chimeric polypeptide (CP), and the ABD-CP fusion was recombinantly synthesized by bacterial expression of the gene. Doxorubicin (DOX) was conjugated to the C-terminus of the ABD-CP fusion, and conjugation of multiple copies of the drug to one end of the ABD-CP triggered its self-assembly into ∼100 nm diameter spherical micelles. ABD-decorated micelles exhibited submicromolar binding affinity for albumin and also preserved their spherical morphology in the presence of albumin. In a murine model, albumin-binding micelles exhibited dose-independent pharmacokinetics, whereas naked micelles exhibited dose-dependent pharmacokinetics. In addition, in a canine model, albumin binding micelles resulted in a 3-fold increase in plasma half-life and 6-fold increase in plasma exposure as defined by the area under the curve (AUC) of the drug, compared with naked micelles. Furthermore, in a murine colon carcinoma model, albumin-binding nanoparticles demonstrated lower uptake by the reticuloendothelial system (RES) system organs, the liver and spleen, that are the main target organs of toxicity for nanoparticulate delivery systems and higher uptake by the tumor than naked micelles. The increased uptake by s.c. C26 colon carcinoma tumors in mice translated to a wider therapeutic window of doses ranging from 20 to 60 mg equivalent of DOX per kg body weight (mg DOX equiv·kg-1 BW) for albumin-binding ABD-CP-DOX micelles, as compared to naked micelles that were only effective at their maximum tolerated dose of 40 mg DOX equiv·kg-1 BW.}, number={12}, journal={NANO LETTERS}, author={Yousefpour, Parisa and McDaniel, Jonathan R. and Prasad, Varun and Ahn, Lucie and Li, Xinghai and Subrahmanyan, Rishi and Weitzhandler, Isaac and Suter, Steven and Chilkoti, Ashutosh}, year={2018}, month={Dec}, pages={7784–7793} }
 @article{ross_nemec_kapatos_miller_holmes_suter_buntzman_soderblom_collins_hess_et al._2018, title={The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif}, volume={197}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/J.VETIMM.2018.01.005}, DOI={10.1016/J.VETIMM.2018.01.005}, abstractNote={Ideally, CD8+ T-cell responses against virally infected or malignant cells are defined at the level of the specific peptide and restricting MHC class I element, a determination not yet made in the dog. To advance the discovery of canine CTL epitopes, we sought to determine whether a putative classical MHC class Ia gene, Dog Leukocyte Antigen (DLA)-88, presents peptides from a viral pathogen, canine distemper virus (CDV). To investigate this possibility, DLA-88*508:01, an allele prevalent in Golden Retrievers, was expressed as a FLAG-tagged construct in canine histiocytic cells to allow affinity purification of peptide-DLA-88 complexes and subsequent elution of bound peptides. Pattern analysis of self peptide sequences, which were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), permitted binding preferences to be inferred. DLA-88*508:01 binds peptides that are 9-to-12 amino acids in length, with a modest preference for 9- and 11-mers. Hydrophobic residues are favored at positions 2 and 3, as are K, R or F residues at the C-terminus. Testing motif-matched and -unmatched synthetic peptides via peptide-MHC surface stabilization assay using a DLA-88*508:01-transfected, TAP-deficient RMA-S line supported these conclusions. With CDV infection, 22 viral peptides ranging from 9-to-12 residues in length were identified in DLA-88*508:01 eluates by LC-MS/MS. Combined motif analysis and surface stabilization assay data suggested that 11 of these 22 peptides, derived from CDV hemagglutinin, large polymerase, matrix, nucleocapsid, and V proteins, were processed and presented, and thus, potential targets of anti-viral CTL in DLA-88*508:01-bearing dogs. The presentation of diverse self and viral peptides indicates that DLA-88 is a classical MHC class Ia gene.}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Ross, Peter and Nemec, Paige S. and Kapatos, Alexander and Miller, Keith R. and Holmes, Jennifer C. and Suter, Steven E. and Buntzman, Adam S. and Soderblom, Erik J. and Collins, Edward J. and Hess, Paul and et al.}, year={2018}, month={Mar}, pages={76–86} }
 @article{mastromauro_suter_hauck_hess_2017, title={Oral melphalan for the treatment of relapsed canine lymphoma}, volume={16}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12356}, DOI={10.1111/vco.12356}, abstractNote={Oral melphalan has been included in multi‐agent rescue protocols for canine lymphoma but its activity as a single‐agent for this purpose has not been established. Inexpensive cost, ease of administration and tolerability make oral melphalan an attractive candidate for single‐agent rescue therapy of canine lymphoma. Retrospective evaluation of 19 cases of relapsed canine lymphoma treated with oral melphalan was performed. Melphalan was primarily administered (n = 16) via a high dose protocol (HDM) with a median dosage of 19.4 mg m−2. Fifteen dogs (78.9%) were treated concurrently with corticosteroids. Response evaluation was possible for all dogs with a calculated overall clinical benefit (partial response [PR] + stable disease [SD]) of 31.6% (PR 3/19; SD 3/19). Times to progression following melphalan (TTP‐M) were 14, 24 and 34 days for responders and 20, 28 and 103 days for dogs experiencing SD. Twelve of 17 dogs evaluable for toxicity experienced an adverse event (AE) with only 3 dogs experiencing a grade III or higher AE. Haematologic toxicity was common (11/17) while gastrointestinal toxicity was rare (1/17). Although treatment resulted in limited clinical benefit and non‐durable responses, oral melphalan was well‐tolerated and may be a reasonable rescue option in cases where minimal effective agents remain.}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Mastromauro, M. L. and Suter, S. E. and Hauck, M. L. and Hess, P. R.}, year={2017}, month={Sep}, pages={E123–E129} }
 @article{saba_paoloni_mazcko_kisseberth_burton_smith_wilson-robles_allstadt_vail_henry_et al._2016, title={A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model}, volume={11}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0149194}, abstractNote={Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10–70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.}, number={2}, journal={PLOS ONE}, author={Saba, Corey and Paoloni, Melissa and Mazcko, Christina and Kisseberth, William and Burton, Jenna H. and Smith, Annette and Wilson-Robles, Heather and Allstadt, Sara and Vail, David and Henry, Carolyn and et al.}, year={2016}, month={Feb} }
 @article{bennett_williams_ferguson_hauck_suter_lanier_hess_2016, title={Canine acute leukaemia: 50 cases (1989-2014)}, volume={15}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/vco.12251}, DOI={10.1111/vco.12251}, abstractNote={AbstractAcute leukaemia (AL) is a bone marrow malignancy of hematopoietic progenitors that historically is poorly responsive to treatment. With the widespread adoption of dose‐intense chemotherapy, more human patients attain long‐term survivals, but whether comparable progress has been made in canine AL is unknown. To investigate this question, medical records from three academic veterinary hospitals were reviewed. Fifty dogs met the criteria for AL, having excess circulating or marrow blasts, a major cytopenia(s), and no substantial lymphadenopathy. Thirty‐six dogs received cytotoxic chemotherapy; 23 achieved a complete or partial response for a median of 56 days (range, 9–218). With failure or relapse, 14 dogs were rescued. Median survival with treatment was poor at 55 days (range, 1–300). Untreated (n = 6) and palliatively‐treated (n = 8) dogs lived a median of 7.5 days. Most dogs developed chemoresistance within weeks of initiating treatment, and consequently, survival times for AL remain disappointingly short.}, number={3}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Bennett, A. L. and Williams, L. E. and Ferguson, M. W. and Hauck, M. L. and Suter, S. E. and Lanier, C. B. and Hess, P. R.}, year={2016}, month={Jul}, pages={1101–1114} }
 @article{roode_rotroff_richards_moore_motsinger-reif_okamura_mizuno_tsujimoto_suter_breen_2016, title={Comprehensive genomic characterization of five canine lymphoid tumor cell lines}, volume={12}, journal={BMC Veterinary Research}, author={Roode, S. C. and Rotroff, D. and Richards, K. L. and Moore, P. and Motsinger-Reif, A. and Okamura, Y. and Mizuno, T. and Tsujimoto, H. and Suter, S. E. and Breen, M.}, year={2016} }
 @article{meichner_fogle_english_suter_2016, title={Expression of Apoptosis-regulating Proteins Bcl-2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma}, volume={30}, ISSN={["1939-1676"]}, DOI={10.1111/jvim.13937}, abstractNote={BackgroundDysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs.Hypothesis/ObjectivesThat Bcl‐2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl‐2/Bax ratio is correlated with prognosis.AnimalsFifty‐five client‐owned dogs with multicentric lymphoma and 5 healthy dogs.MethodsProspective, case–control study. We compared 3 methods (flow cytometry, qRT‐PCR, Western blot) for Bcl‐2 and Bax quantification in a subset of dogs. The effect of time on Bcl‐2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl‐2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression‐free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment.ResultsBcl‐2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl‐2/Bax ratio was higher in dogs with T‐cell lymphoma (TCL; median 0.97, range 0.37–1.36) compared to B‐cell lymphoma (BCL; median 0.36, range 0.07–1.45) (P < .0001) and normal dogs (median 0.36, range 0.21–0.48) (P = .0006), respectively. Dogs with Bcl‐2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19).Conclusions and clinical importanceHigher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl‐2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies.}, number={3}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Meichner, K. and Fogle, J. E. and English, L. and Suter, S. E.}, year={2016}, pages={819–826} }
 @article{applegate_troan_chen_suter_2017, title={Surgical Management of Colonic Adenocarcinoma in a Rat (Rattus norvegicus)}, volume={26}, ISSN={1557-5063}, url={http://dx.doi.org/10.1053/j.jepm.2016.10.011}, DOI={10.1053/j.jepm.2016.10.011}, abstractNote={Abstract A 9-month-old female Dumbo rat ( Rattus norvegicus ) was evaluated for a 24-hour history of obstipation. A general physical examination revealed a large irregular abdominal mass, extending caudally from mid-abdomen to the pelvis. The mass had a firm central region with a compressible periphery. Radiographic imaging confirmed severe intestinal distention, but failed to delineate a discrete mass. Following 3 days of unsuccessful medical therapy for possible colonic impaction, surgical intervention was elected. A colocolic resection and anastomosis was completed to remove 7cm of the colon, including the 5cm mass and 1cm of grossly normal appearing colon proximal and distal to the mass. Histology confirmed colonic adenocarcinoma. The rat lived for 2 years, following colonic resection and anastomosis, uncomplicated by gastrointestinal neoplasia or metastatic disease and was euthanized due to unrelated quality of life issues. Necropsy revealed no evidence of colonic tumor recurrence or metastatic disease.}, number={1}, journal={Journal of Exotic Pet Medicine}, publisher={Elsevier BV}, author={Applegate, Jeffrey R., Jr and Troan, Brigid V. and Chen, Laura R. and Suter, Steven E.}, year={2017}, month={Jan}, pages={47–52} }
 @article{suter_hamilton_sullivan_venkataraman_2015, title={Allogeneic hematopoietic cell transplantation in a dog with acute large granular lymphocytic leukemia}, volume={246}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.246.9.994}, DOI={10.2460/javma.246.9.994}, abstractNote={Abstract
Case Description—A 3-year-old 10-kg (22-lb) neutered male Cavalier King Charles Spaniel was referred because of an episode of acute vomiting and diarrhea.
Clinical Findings—On physical examination, mild splenomegaly and prominent submandibular and popliteal lymph nodes were detected. Complete blood cell count revealed a high WBC count, characterized by a moderate lymphocytosis with 62% unclassified cells and severe thrombocytopenia with macroplatelets. On cytologic evaluation, the unclassified cells were described as large, neoplastic lymphoid cells containing a large nucleus with lacy chromatin and a large amount of blue vacuolated cytoplasm containing sparse, very fine azurophilic granules. A diagnosis of acute large granular lymphocytic leukemia of splenic origin was made.
Treatment and Outcome—Following induction chemotherapy, the affected dog underwent allogeneic hematopoietic cell transplantation with dog leukocyte antigen–matched CD34+ cells harvested from a sibling of the same litter. Chimerism analysis revealed full donor engraftment within 2 weeks after transplantation that remained stable for at least 2 years, with the dog remaining apparently healthy at home.
Clinical Relevance—Acute leukemias in dogs are rapidly fatal diseases. If an appropriate donor can be located, allogeneic hematopoietic cell transplantation may offer a feasible treatment, although peripheral blood CD34+ cell harvesting requires the availability of cell separator machines and management of graft-versus-host disease with immunosuppressive agents.}, number={9}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Suter, Steven E. and Hamilton, Matthew J and Sullivan, Edmund W and Venkataraman, Gopalakrishnan M}, year={2015}, month={May}, pages={994–997} }
 @article{fogle_tarigo_thalheim_williams_english_suter_2015, title={CD45+ and CD45− lymphocyte populations identified by flow cytometry from dogs with lymphoma exhibit similar morphology and the same clonal (B cell or T cell) lineage}, volume={168}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2015.10.004}, DOI={10.1016/j.vetimm.2015.10.004}, abstractNote={Flow cytometric analysis of canine lymphoma sometimes demonstrates a mixed population of CD45+ and CD45- lymphocytes. Recently, indolent forms of canine lymphoma have been described which are associated with the loss of CD45 expression, warranting further investigation of the role of CD45 in canine lymphoma. The purpose of this study was to compare morphology and assess clonal origin between CD45+ and CD45- lymphocyte populations identified by flow cytometry in confirmed cases of canine B- and T-cell lymphoma. Our hypothesis was that the CD45- population of lymphocytes represented a phenotypic variant of the CD45+ population. Fifteen client-owned dogs with lymphoma and distinct CD45+ and CD45- lymphocyte populations identified by flow cytometry were identified for a blinded, prospective assessment of morphology and clonal origin (B cell or T cell) between populations of sorted CD45+ and CD45- cells. Lymphocytes were isolated from 11 dogs for paired cytologic evaluation. In 10/11 dogs, the CD45+ and CD45- samples were similar (95% C.I., 0.301-1.00). DNA was harvested from sorted populations of CD45+ and CD45- cells from 12/15 dogs and PARR analysis produced amplicons of identical size from both populations, indicating that 100% (12/12) were of the same lineage, B cell or T cell (95% C.I., 0.757-1.00). Collectively, our data suggests that the CD45- population identified in dogs with lymphoma represents a phenotypic variant of the CD45+ population.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Fogle, J.E. and Tarigo, J.L. and Thalheim, L. and Williams, L.E. and English, L.B. and Suter, S.E.}, year={2015}, month={Dec}, pages={242–248} }
 @article{roode_rotroff_avery_suter_bienzle_schiffman_motsinger-reif_breen_2015, title={Genome-wide assessment of recurrent genomic imbalances in canine leukemia identifies evolutionarily conserved regions for subtype differentiation}, volume={23}, ISSN={0967-3849 1573-6849}, url={http://dx.doi.org/10.1007/s10577-015-9475-7}, DOI={10.1007/s10577-015-9475-7}, abstractNote={Leukemia in dogs is a heterogeneous disease with survival ranging from days to years, depending on the subtype. Strides have been made in both human and canine leukemia to improve classification and understanding of pathogenesis through immunophenotyping, yet classification and choosing appropriate therapy remains challenging. In this study, we assessed 123 cases of canine leukemia (28 ALLs, 24 AMLs, 25 B-CLLs, and 46 T-CLLs) using high-resolution oligonucleotide array comparative genomic hybridization (oaCGH) to detect DNA copy number alterations (CNAs). For the first time, such data were used to identify recurrent CNAs and inclusive genes that may be potential drivers of subtype-specific pathogenesis. We performed predictive modeling to identify CNAs that could reliably differentiate acute subtypes (ALL vs. AML) and chronic subtypes (B-CLL vs. T-CLL) and used this model to differentiate cases with up to 83.3 and 95.8 % precision, respectively, based on CNAs at only one to three genomic regions. In addition, CGH datasets for canine and human leukemia were compared to reveal evolutionarily conserved copy number changes between species, including the shared gain of HSA 21q in ALL and ∼25 Mb of shared gain of HSA 12 and loss of HSA 13q14 in CLL. These findings support the use of canine leukemia as a relevant in vivo model for human leukemia and justify the need to further explore the conserved genomic regions of interest for their clinical impact.}, number={4}, journal={Chromosome Research}, publisher={Springer Science and Business Media LLC}, author={Roode, Sarah C. and Rotroff, Daniel and Avery, Anne C. and Suter, Steven E. and Bienzle, Dorothee and Schiffman, Joshua D. and Motsinger-Reif, Alison and Breen, Matthew}, year={2015}, month={Jun}, pages={681–708} }
 @misc{suter_2015, title={Questions diagnosis of acute large granular lymphocytic leukemia response}, volume={247}, number={1}, journal={Journal of the American Veterinary Medical Association}, author={Suter, S.}, year={2015}, pages={37–38} }
 @article{warry_willcox_suter_2014, title={Autologous Peripheral Blood Hematopoietic Cell Transplantation in Dogs with T-Cell Lymphoma}, volume={28}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12302}, DOI={10.1111/jvim.12302}, abstractNote={BackgroundPeripheral blood hematopoietic cell transplantation (PBHCT) is a feasible treatment option for dogs with B‐cell lymphoma.ObjectiveTo examine apheresis and PBHCT outcomes in dogs diagnosed with T‐cell lymphoma (TCL).AnimalsFifteen client‐owned dogs diagnosed with high‐grade TCL.MethodsAfter high‐dose cyclophosphamide and rhG‐colony‐stimulating (rhG‐CSF) factor treatment, peripheral blood mononuclear cells were collected using cell separators. The harvested cells then were infused after varying doses of total body irradiation (TBI). Postirradiation adverse effects were managed symptomatically and dogs were discharged upon evidence of hematopoietic engraftment.ResultsMore than 2 × 106 CD34+ cells/kg were harvested from 15/15 dogs. Thirteen of 15 (87%) dogs engrafted appropriately, whereas 2 (13%) of the dogs died in the hospital. One dog developed cutaneous B‐cell lymphoma 120 days post‐PBHCT. The median disease‐free interval and overall survival (OS) of the 13 dogs transplanted in first remission from the time of PBHCT were 184 and 240 days, respectively. Stage and substage of disease at diagnosis had no effect on OS. Two of 13 (15%) dogs were alive 741 and 772 days post‐PBHCT.Conclusions and Clinical ImportancePBHCT may be considered as a treatment option for dogs with TCL.}, number={2}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Warry, E.E. and Willcox, J.L. and Suter, S.E.}, year={2014}, month={Jan}, pages={529–537} }
 @article{bucknoff_hanel_marks_motsinger-reif_suter_2014, title={Evaluation of thromboelastography for prediction of clinical bleeding in thrombocytopenic dogs after total body irradiation and hematopoietic cell transplantation}, volume={75}, ISSN={["1943-5681"]}, DOI={10.2460/ajvr.75.5.425}, abstractNote={Abstract
Objective—To determine whether thromboelastography is more accurate than conventional methods of evaluating hemostasis for the prediction of clinical bleeding in thrombocytopenic dogs following total body irradiation (TBI) and bone marrow transplantation (BMT).
Animals—10 client-owned thrombocytopenic dogs with multicentric lymphoma.
Procedures—Results of a kaolin-activated thromboelastography assay, platelet count, and buccal mucosal bleeding time were evaluated for correlation to clinical bleeding.
Results—Maximum amplitude, derived via thromboelastography, was the only hemostatic variable with significant correlation to clinical bleeding. Buccal mucosal bleeding time had a high sensitivity but poor specificity for identifying dogs with clinical bleeding.
Conclusions and Clinical Relevance—Compared with buccal mucosal bleeding time and platelet count, thromboelastography was more reliable at identifying thrombocytopenic dogs with a low risk of bleeding and could be considered to help guide the use of transfusion products in dogs undergoing TBI and BMT.}, number={5}, journal={AMERICAN JOURNAL OF VETERINARY RESEARCH}, author={Bucknoff, Melissa C. and Hanel, Rita M. and Marks, Steven L. and Motsinger-Reif, Alison A. and Suter, Steven E.}, year={2014}, month={May}, pages={425–432} }
 @article{richards_suter_2014, title={Man's best friend: what can pet dogs teach us about non-Hodgkin's lymphoma?}, volume={263}, ISSN={0105-2896}, url={http://dx.doi.org/10.1111/imr.12238}, DOI={10.1111/imr.12238}, abstractNote={SummaryAnimal models are essential for understanding lymphoma biology and testing new treatments prior to human studies. Spontaneously arising lymphomas in pet dogs represent an underutilized resource that could be used to complement current mouse lymphoma models, which do not adequately represent all aspects of the human disease. Canine lymphoma resembles human lymphoma in many important ways, including characteristic translocations and molecular abnormalities and similar therapeutic responses to chemotherapy, radiation, and newer targeted therapies (e.g. ibrutinib). Given the large number of pet dogs and high incidence of lymphoma, particularly in susceptible breeds, dogs represent a largely untapped resource for advancing the understanding and treatment of human lymphoma. This review highlights similarities in molecular biology, diagnosis, treatment, and outcomes between human and canine lymphoma. It also describes resources that are currently available to study canine lymphoma, advantages to be gained by exploiting the genetic breed structure in dogs, and current and future challenges and opportunities to take full advantage of this resource for lymphoma studies.}, number={1}, journal={Immunological Reviews}, publisher={Wiley}, author={Richards, Kristy L. and Suter, Steven E.}, year={2014}, month={Dec}, pages={173–191} }
 @article{posner_willcox_suter_2013, title={Apheresis in three dogs weighing <14 kg}, volume={40}, ISSN={1467-2987}, url={http://dx.doi.org/10.1111/vaa.12026}, DOI={10.1111/vaa.12026}, abstractNote={HISTORY
CaridianBCT apheresis machines require a ~285 mL priming volume (extracorporeal blood) that is withdrawn from the patient in ~10 minutes. Therefore, apheresis in dogs has generally been limited to dogs > ~20 kg to assure <20% of the blood volume is removed in the priming phase. ANIMALS/PHYSICAL EXAMINATION: Three dogs weighing <14 kg (13.6, 10.5, and 9.9 kg) with lymphoma that underwent apheresis.


MANAGEMENT
The dogs were premedicated for placement of apheresis catheters with hydromorphone (0.1 mg kg(-1) ) IM. Anesthesia was induced with propofol, to effect, intravenously and general anesthesia was maintained with isoflurane in oxygen. Following catheter placement, dogs were allowed to recover from isoflurane but were kept sedated with either a dexmedetomidine constant rate infusion (CRI) or a propofol CRI. Real time autologous blood priming was not performed in any of the dogs. Instead, priming solutions were composed of a combination of hetastarch, lactated Ringer's solution, and/or autologous blood that was harvested 4 days before the procedure. During apheresis, dogs received anticoagulant citrate-dextrose, solution-A (ACD-A) to prevent clotting and 10% calcium gluconate as needed to maintain normal ionized calcium concentrations. Dogs were monitored for cardiovascular and cardiopulmonary stability, anemia and lactic acidosis.


FOLLOW-UP
All of the dogs had cardiovascular and cardiopulmonary values within clinically acceptable ranges. Immediately following apheresis all of the dogs were mildly to moderately anemic (PCV; 17-35%) although none of the dogs required a transfusion or had an increased lactate concentration.


CONCLUSIONS
Dogs as small as 9.9 kg can successfully undergo apheresis with a variety of priming solutions. Dexmedetomidine or propofol given as a CRI provides sufficient sedation for this procedure.}, number={4}, journal={Veterinary Anaesthesia and Analgesia}, publisher={Elsevier BV}, author={Posner, Lysa P and Willcox, Jennifer L and Suter, Steven E}, year={2013}, month={Jul}, pages={403–409} }
 @article{kim_d'costa_suter_kim_2013, title={Evaluation of a side population of canine lymphoma cells using Hoechst 33342 dye}, volume={14}, ISSN={["1976-555X"]}, DOI={10.4142/jvs.2013.14.4.481}, abstractNote={Cancer stem cell (CSC) research has increased exponentially to gain further insight into the mechanisms underlying both carcinogenesis and chemotherapy resistance. The present study was performed to explore the potential value of a side population (SP) assay for identifying and characterizing putative CSCs among canine lymphoma cells. Canine lymphoma cells from cell lines and clinical samples were subjected to the SP assay consisting of Hoechst 33342 staining and subsequent flow cytometric analysis. The SP assay revealed various amounts of a SP fraction among the canine lymphoma cells. The percentages of SP were not affected by inhibitors of membrane transporters, verapamil hydrochloride, or fumitremorgin C. Most of the canine lymphoma cells expressed high levels of Bmi-1 and membrane transporter proteins such as ABCG2 and phosphorylated (p)-glycoprotein. This investigation lays the groundwork for further studies of the biological behaviors and molecular characteristics of CSCs in cases of canine lymphoma.}, number={4}, journal={JOURNAL OF VETERINARY SCIENCE}, author={Kim, Myung-Chul and D'Costa, Susan and Suter, Steven and Kim, Yongbaek}, year={2013}, month={Dec}, pages={481–486} }
 @article{smallwood_small_suter_richards_2013, title={Expression of asparagine synthetase predictsin vitroresponse tol-asparaginase in canine lymphoid cell lines}, volume={55}, ISSN={1042-8194 1029-2403}, url={http://dx.doi.org/10.3109/10428194.2013.842980}, DOI={10.3109/10428194.2013.842980}, abstractNote={Abstract l-asparaginase (L-asp), a bacterial enzyme that depletes extracellular asparagine, is used to treat acute lymphoblastic leukemia in humans and a variety of aggressive lymphoid malignancies in dogs. Resistance to this drug is an important cause of treatment failure in both species. Using canine lymphoid cell lines, we found that L-asp sensitivity is strongly negatively correlated with the level of methylation of the asparagine synthetase (ASNS) promoter. Selection for in vitro resistance was accompanied by increased ASNS promoter methylation and decreased ASNS mRNA expression. In addition, treatment with the hypomethylating agent 5-azacytidine increased resistance to L-asp. ASNS methylation and expression is not predictive of overall survival or progression-free survival in canine lymphoma patients treated with L-asp. Our data suggest that ASNS is an important factor in mediating the in vitro response of canine lymphoid cells to L-asp; however, resistance mechanisms may be more complex in dogs treated clinically with L-asp, potentially due to concurrent treatments.}, number={6}, journal={Leukemia & Lymphoma}, publisher={Informa UK Limited}, author={Smallwood, Tangi L. and Small, George W. and Suter, Steven E. and Richards, Kristy L.}, year={2013}, month={Nov}, pages={1357–1365} }
 @article{richards_motsinger-reif_chen_fedoriw_fan_nielsen_small_thomas_smith_dave_et al._2013, title={Gene Profiling of Canine B-Cell Lymphoma Reveals Germinal Center and Postgerminal Center Subtypes with Different Survival Times, Modeling Human DLBCL}, volume={73}, ISSN={0008-5472 1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.CAN-12-3546}, DOI={10.1158/0008-5472.can-12-3546}, abstractNote={Abstract
               Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype, and fewer than half of patients are cured with standard first-line therapy. To improve therapeutic options, better animal models that accurately mimic human DLBCL (hDLBCL) are needed. Canine DLBCL, one of the most common cancers in veterinary oncology, is morphologically similar to hDLBCL and is treated using similar chemotherapeutic protocols. With genomic technologies, it is now possible to molecularly evaluate dogs as a potential large-animal model for hDLBCL. We evaluated canine B-cell lymphomas (cBCL) using immunohistochemistry (IHC) and gene expression profiling. cBCL expression profiles were similar in many ways to hDLBCLs. For instance, a subset had increased expression of NF-κB pathway genes, mirroring human activated B-cell (ABC)–type DLBCL. Furthermore, immunoglobulin heavy chain ongoing mutation status, which is correlated with ABC/germinal center B-cell cell of origin in hDLBCL, separated cBCL into two groups with statistically different progression-free and overall survival times. In contrast with hDLBCL, cBCL rarely expressed BCL6 and MUM1/IRF4 by IHC. Collectively, these studies identify molecular similarities to hDLBCL that introduce pet dogs as a representative model of hDLBCL for future studies, including therapeutic clinical trials. Cancer Res; 73(16); 5029–39. ©2013 AACR.}, number={16}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Richards, K. L. and Motsinger-Reif, A. A. and Chen, H.-W. and Fedoriw, Y. and Fan, C. and Nielsen, D. M. and Small, G. W. and Thomas, R. and Smith, C. and Dave, S. S. and et al.}, year={2013}, month={Jun}, pages={5029–5039} }
 @article{su_nielsen_zhu_richards_suter_breen_motsinger-reif_osborne_2013, title={Gene selection and cancer type classification of diffuse large-B-cell lymphoma using a bivariate mixture model for two-species data}, volume={7}, journal={Human Genomics}, author={Su, Y. H. and Nielsen, D. and Zhu, L. and Richards, K. and Suter, S. and Breen, M. and Motsinger-Reif, A. and Osborne, J.}, year={2013} }
 @article{thalheim_williams_borst_fogle_suter_2013, title={Lymphoma Immunophenotype of Dogs Determined by Immunohistochemistry, Flow Cytometry, and Polymerase Chain Reaction for Antigen Receptor Rearrangements}, volume={27}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/jvim.12185}, DOI={10.1111/jvim.12185}, abstractNote={BackgroundImmunohistochemistry (IHC), flow cytometry (FC), and PCR for antigen receptor rearrangements (PARR) are 3 widely utilized tests to determine immunophenotype in dogs with lymphoma (LSA).ObjectivesThis study evaluated the ability of FC and PARR to correctly predict immunophenotype as defined by IHC and to determine the level of agreement among the 3 tests.AnimalsSixty‐two dogs with lymphoma.MethodsRetrospective study. Medical records were searched to identify dogs with LSA that had concurrent IHC, FC, and PARR performed. Immunophenotype results were categorized as B‐cell, T‐cell, dual immunophenotype (B‐ and T‐cell), or indeterminate. The results of FC and PARR were evaluated for correctly classifying B‐ and T‐cell LSA as compared with IHC. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were evaluated in addition to concordance between each test.ResultsThe sensitivity of FC was significantly higher than PARR for both B‐cell (91% versus 67%; P < 0.0072) and T‐cell (100% versus 75%; P < 0.0312) LSA. The percent agreement between FC and IHC was 94%, between PARR and IHC was 69%, between FC and PARR was 63%, and among all 3 tests was 63%.Conclusions and Clinical ImportanceFlow cytometry is superior to PARR in correctly predicting immunophenotype when evaluating lymph nodes from dogs already diagnosed with B‐ or T‐cell LSA. If fresh samples are not available for FC, PARR is an acceptable assay for determination of immunophenotype given its high specificity.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Thalheim, L. and Williams, L.E. and Borst, L.B. and Fogle, J.E. and Suter, S.E.}, year={2013}, month={Sep}, pages={1509–1516} }
 @article{chen_small_motsinger-reif_suter_richards_2014, title={VH1-44 gene usage defines a subset of canine B-cell lymphomas associated with better patient survival}, volume={157}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2013.10.020}, DOI={10.1016/j.vetimm.2013.10.020}, abstractNote={The use of specific immunoglobulin heavy chain variable region (VH) genes has been associated with increased patient survival in human B-cell lymphomas (hBCL). Given the similarity of human and canine BCL (cBCL) in morphology and clinical treatment, we examined the choice of VH in cBCL and determined whether VH gene selection was a distinct feature associated with survival time in dogs. VH gene selection and mutational status in 52 cBCL, including 29 diffuse large B-cell lymphomas (cDLBCL, the most common subtype of cBCL), were analyzed by comparison with the 80 published canine germline VH gene sequences. We further examined the prognostic impact of the subgroups defined by these features on canine survival. We found that VH1-44 was preferentially expressed in the majority of the 52 cBCLs (60%) as well as in the majority of the cDLBCL subset (59%). VH1-44 gene expression was associated with a statistically better overall survival (p=0.039) in cBCL patients, as well as in the cDLBCL subset of patients (p=0.038). These findings suggest that VH gene selection in cBCL is not random and may therefore have functional implications for cBCL lymphomagenesis, in addition to being a useful prognostic biomarker.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Chen, Hsiao-Wei and Small, George W. and Motsinger-Reif, Alison and Suter, Steven E. and Richards, Kristy L.}, year={2014}, month={Feb}, pages={125–130} }
 @article{miller_thompson_suter_fogle_2013, title={CD8+ clonality is associated with prolonged acute plasma viremia and altered mRNA cytokine profiles during the course of Feline Immunodeficiency Virus infection}, volume={152}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2012.12.005}, DOI={10.1016/j.vetimm.2012.12.005}, abstractNote={Acute lentiviral infection is characterized by early CD8(+) cytotoxic T cell (CTL) activity and a subsequent decline in plasma viremia. However, CD8(+) lymphocytes fail to eliminate the virus and a progressive T cell immune dysfunction develops during the course of chronic lentiviral infection. To further define this CD8(+) immune dysfunction we utilized PARR (PCR for antigen receptor rearrangements), a technique which measures clonally expanded lymphocyte populations by comparison of highly conserved T cell receptor (TCR) regions to identify the prevalence of clonal CD8(+) T cells following FIV infection. We then compared phenotype, mRNA profiles, CD8(+) proliferation and plasma viremia during acute and chronic infection for PARR positive (PARR(+)) and PARR negative (PARR(-)) Feline Immunodeficiency Virus (FIV) infected cats. We demonstrated that approximately forty percent of the FIV(+) cats examined exhibit CD8(+) clonality compared to none of the FIV(-) control cats. There were no phenotypic differences between PARR(+) and PARR(-) CD8(+) lymphocytes from FIV(+) cats but retrospective analysis of plasma viremia over the course of infection revealed a delayed peak in plasma viremia and a decline in lymphocyte counts were observed in the PARR(+) group during acute infection. CD8(+) lymphocytes isolated from chronically infected PARR(-) cats exhibited significantly higher mRNA expression of IFN-γ and IL-2 following mitogenic stimulation when compared to PARR(+) CD8(+) lymphocytes. These data suggest that clonal CD8(+) expansion may be related to impaired control of acute viremia and less effective CD8(+) anti-viral function. Using PARR to assess changes in CD8(+) clonality during the progression from acute to chronic FIV infection may help to better characterize the factors which contribute to CD8(+) anergy and lentiviral persistence.}, number={3-4}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Miller, Michelle M. and Thompson, Elizabeth M. and Suter, Steven E. and Fogle, Jonathan E.}, year={2013}, month={Apr}, pages={200–208} }
 @article{shiomitsu_bauer_grasperge_suter_waite_2012, title={Cutaneous epitheliotropic lymphoma with dual CD3 and c-kit expression in a dog}, volume={41}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165x.2012.00477.x}, abstractNote={AbstractAn 11‐year‐old 8.9‐kg spayed female Boston Terrier was presented for evaluation of a mucocutaneous tumor on the right side of the upper lip that had been biopsied (punch biopsy) by the referring veterinarian. The histologic diagnosis was poorly differentiated round cell tumor involving the submucosa with patchy involvement of the mucosa. On presentation of the dog to Louisiana State University, the tumor was found to involve the mucosa and haired skin surface of the right upper lip. A fine‐needle aspirate of the right mandibular lymph node contained atypical poorly differentiated round cells similar to those in the histologic sections. To further characterize the tumor, immunohistochemical analysis of the tumor on the lip was performed; tumor cells were strongly immunoreactive for both CD3 and c‐kit in a cytoplasmic to membranous pattern, with CD3 expression having a more intense membranous component. The diagnosis was cutaneous epitheliotropic T‐cell lymphoma with co‐expression of CD3 and c‐kit by neoplastic lymphocytes, an unusual finding. As receptor tyrosine kinases can be attractive targets for cancer treatment, expression of these molecular targets in tumors is a promising subject of future research.}, number={4}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Shiomitsu, Keijiro and Bauer, Rudy W. and Grasperge, Britton J. and Suter, Steven E. and Waite, Kyle J.}, year={2012}, month={Dec}, pages={594–598} }
 @article{suter_2011, title={Collection of Peripheral Blood CD34+ Progenitor Cells from Healthy Dogs and Dogs Diagnosed with Lymphoproliferative Diseases Using a Baxter-Fenwal CS-3000 Plus Blood Cell Separator}, volume={25}, ISSN={0891-6640}, url={http://dx.doi.org/10.1111/j.1939-1676.2011.00827.x}, DOI={10.1111/j.1939-1676.2011.00827.x}, abstractNote={BackgroundCanine peripheral blood mononuclear cell (PBMC) apheresis using a Baxter‐Fenwal CS‐3000 Plus automated blood cell separator has not been reported.ObjectiveTo determine the feasibility and safety of using a CS‐3000 Plus blood cell separator with a small volume separation container holder (SVSCH) and small volume collection chamber (SVCC) to harvest canine PBMCs from dogs weighing <50 kg.AnimalsEight healthy mongrel dogs and 11 client‐owned dogs in clinical remission for lymphoproliferative diseases (LPD).MethodsIn this prospective study, aphereses were performed using a Baxter‐Fenwal CS‐3000 Plus blood cell separator, with or without recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) treatment.ResultsAphereses from 6 healthy dogs given rhG‐CSF yielded an average of 1.1 × 107 ± 8.2 × 106 CD34+ cells/kg. Aphereses from LPD dogs given rhG‐CSF yielded an average of 5.4 × 106 ± 3.25 × 106 CD34+ cells/kg (P = .17). Higher hematocrit in both groups of dogs receiving rhG‐CSF correlated with an increased number of CD34+ cells/kg harvested (healthy, P = .04; LPD, P = .05). Apheresis was well tolerated by all dogs.Conclusions and Clinical ImportanceCanine PBMC apheresis using the Baxter‐Fenwal CS‐3000 Plus cell separator with an SVSCH and SVCC is a feasible and safe option for harvesting an adequate number of CD34+ peripheral blood progenitor cells from dogs weighing ≥17 kg for hematopoietic cell transplantation.}, number={6}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Suter, S.E.}, year={2011}, month={Nov}, pages={1406–1413} }
 @article{pate_gilger_suter_clode_2011, title={Diagnosis of intraocular lymphosarcoma in a dog by use of a polymerase chain reaction assay for antigen receptor rearrangement}, volume={238}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.238.5.625}, DOI={10.2460/javma.238.5.625}, abstractNote={Abstract
Case Description—A 12-year-old castrated male mixed-breed dog was evaluated because of blepharospasm and blindness affecting both eyes.
Clinical Findings—During examination and diagnostic testing of the dog, fine-needle aspirates of splenic nodules were examined microscopically and stage Vb multicentric large-cell lymphosarcoma was identified. Aqueocentesis was performed, and sample analysis revealed intraocular lymphosarcoma; B-cell neoplasia was confirmed by use of a PCR assay for antigen receptor rearrangement (PARR) performed on samples of aqueous humor. Secondary uveitis and glaucoma were detected bilaterally in addition to chronic superficial corneal ulcerations in the left eye.
Treatment and Outcome—Treatment for abdominal and intraocular lymphosarcoma involving administration of vincristine, l-asparaginase, cyclophosphamide, doxorubicin, and prednisone was initiated. Secondary uveitis and glaucoma were controlled with topical treatment; however, the corneal ulceration did not resolve. Seven weeks following diagnosis, the dog died as a result of complications related to systemic neoplasia and chemotherapy.
Clinical Relevance—In the dog of this report, intraocular lymphosarcoma was diagnosed via PARR performed on samples of aqueous humor. Moreover, the immunophenotype of the neoplastic cells was determined by use of that diagnostic technique. Because secondary uveitis is a common finding in dogs and cats with systemic lymphosarcoma, intraocular lymphosarcoma should be considered as a differential diagnosis; furthermore, investigation (eg, PARR performed on aqueous humor samples) to identify the presence of intraocular lymphosarcoma is warranted, thereby allowing targeted interventions to be considered in management of those patients.}, number={5}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Pate, Diana O. and Gilger, Brian C. and Suter, Steven E. and Clode, Alison B.}, year={2011}, month={Mar}, pages={625–630} }
 @article{suter_small_seiser_thomas_breen_richards_2011, title={FLT3 mutations in canine acute lymphocytic leukemia}, volume={11}, ISSN={["1471-2407"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-79251575882&partnerID=MN8TOARS}, DOI={10.1186/1471-2407-11-38}, abstractNote={Abstract
          
            Background
            FMS-like tyrosine kinase 3 (FLT3) is a commonly mutated protein in a variety of human acute leukemias. Mutations leading to constitutively active FLT3, including internal tandem duplications of the juxtamembrane domain (ITD), result in continuous cellular proliferation, resistance to apoptotic cell death, and a poorer prognosis. A better understanding of the molecular consequences of FLT3 activation would allow improved therapeutic strategies in these patients. Canine lymphoproliferative diseases, including lymphoma and acute leukemias, share evolutionarily conserved chromosomal aberrations and exhibit conserved mutations within key oncogenes when compared to their human counterparts. A small percentage of canine acute lymphocytic leukemias (ALL) also exhibit FLT3 ITD mutations.
          
          
            Methods
            We molecularly characterized FLT3 mutations in two dogs and one cell line, by DNA sequencing, gene expression analysis via quantitative real-time PCR, and sensitivity to the FLT3 inhibitor lestaurtinib via in vitro proliferation assays. FLT 3 and downstream mediators of FLT3 activation were assessed by Western blotting.
          
          
            Results
            The canine B-cell leukemia cell line, GL-1, and neoplastic cells from 2/7 dogs diagnosed cytologically with ALL were found to have FLT3 ITD mutations and FLT3 mRNA up-regulation. Lestaurtinib, a small molecule FLT3 inhibitor, significantly inhibited the growth of GL-1 cells, while not affecting the growth of two other canine lymphoid cell lines without the FLT3 mutation. Finally, western blots were used to confirm the conserved downstream mediators of FLT3 activating mutations.
          
          
            Conclusions
            These results show that ALL and FLT3 biology is conserved between canine and human patients, supporting the notion that canine ALL, in conjunction with the GL-1 cell line, will be useful in the development of a relevant large animal model to aid in the study of human FLT3 mutant leukemias.
          }, journal={BMC CANCER}, author={Suter, Steven E. and Small, George W. and Seiser, Eric L. and Thomas, Rachael and Breen, Matthew and Richards, Kristy L.}, year={2011}, month={Jan} }
 @article{escobar_grindem_neel_suter_2012, title={Hematologic Changes After Total Body Irradiation and Autologous Transplantation of Hematopoietic Peripheral Blood Progenitor Cells in Dogs With Lymphoma}, volume={49}, ISSN={["0300-9858"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84857676739&partnerID=MN8TOARS}, DOI={10.1177/0300985811410721}, abstractNote={ Dogs with and without lymphoma have undergone hematopoietic cell transplantation in a research setting for decades. North Carolina State University is currently treating dogs with B- and T-cell lymphoma in a clinical setting with autologous peripheral blood progenitor cell transplants, using peripheral blood CD34+ progenitor cells harvested using an apheresis machine. Complete blood counts were performed daily for 15 to 19 days posttransplantation to monitor peripheral blood cell nadirs and subsequent CD34+ cell engraftment. This study documents the hematologic toxicities of total body irradiation in 10 dogs and the subsequent recovery of the affected cell lines after peripheral blood progenitor cell transplant, indicating successful CD34+ engraftment. All peripheral blood cell lines, excluding red blood cells, experienced grade 4 toxicities. All dogs had ≥ 500 neutrophils/μl by day 12, while thrombocytopenia persisted for many weeks. All dogs were clinically normal at discharge. }, number={2}, journal={VETERINARY PATHOLOGY}, author={Escobar, C. and Grindem, C. and Neel, J. A. and Suter, S. E.}, year={2012}, month={Mar}, pages={341–343} }
 @article{uhl_krimer_schliekelman_tompkins_suter_2011, title={Identification of Altered MicroRNA Expression in Canine Lymphoid Cell Lines and Cases of B- and T-Cell Lymphomas}, volume={50}, ISSN={["1098-2264"]}, DOI={10.1002/gcc.20917}, abstractNote={AbstractCanine lymphoma is a common spontaneous tumor with many similarities to human lymphoma, and thus has potential to be an important animal model of lymphomagenesis. This study determined that microRNA (miRNA) expression in canine tumors can be assessed using a commercially available human cancer miRNA qPCR array. miRNA expression in six different canine lymphoid cell lines and in naturally occurring canine B‐ and T‐cell lymphomas was compared using RNA harvested from normal canine peripheral blood mononuclear cells (PBMC) and normal lymph nodes (LN) as controls. We found that false discovery rate (FDR) correction for multiple testing after quantile normalization controlled for variation across arrays and that they were the best methods for normalization and statistical analysis. Increases in miRNAs known to upregulate oncogenes (miR19a+b, miR17‐5p) and decreased expression of miRNAs with tumor suppressor functions (miR‐203, miR‐218, and miR‐181a) also seen in human lymphoid malignancies were observed. However, there were few similarities between canine groups. The results of this study indicate that the use of both PBMC and LN cells as controls provides different, but potentially equally important targets for further analysis. Our findings of miRNA dysregulation in canine lymphoid cell lines and clinical cases of lymphoma emphasize the potential of canine lymphoma as an important spontaneous, large animal model of human B‐ and T‐cell lymphomas. © 2011 Wiley‐Liss, Inc.}, number={11}, journal={GENES CHROMOSOMES & CANCER}, author={Uhl, Elizabeth and Krimer, Paula and Schliekelman, Paul and Tompkins, S. Mark and Suter, Steven}, year={2011}, month={Nov}, pages={950–967} }
 @article{seiser_thomas_richards_kathryn kelley_moore_suter_breen_2011, title={Reading between the lines: molecular characterization of five widely used canine lymphoid tumour cell lines}, volume={11}, ISSN={1476-5810}, url={http://dx.doi.org/10.1111/j.1476-5829.2011.00299.x}, DOI={10.1111/j.1476-5829.2011.00299.x}, abstractNote={Molecular characterization of tumour cell lines is increasingly regarded as a prerequisite for defining their validity as models of in vivo neoplasia. We present the first comprehensive catalogue of genomic and transcriptional characteristics of five widely used canine lymphoid tumour cell lines. High‐resolution microarray‐based comparative genomic hybridization defined their unique profiles of genomic DNA copy number imbalance. Multicolour fluorescence in situ hybridization identified aberrant gains of MYC, KIT and FLT3 and deletions of PTEN and CDKN2 in individual cell lines, and also revealed examples of extensive structural chromosome reorganization. Gene expression profiling and RT‐PCR analyses defined the relationship between genomic imbalance and transcriptional dysregulation in each cell line, clarifying their relevance as models of discrete functional pathways with biological and therapeutic significance. In combination, these data provide an extensive resource of molecular data for directing the appropriate use of these cell lines as tools for studying canine lymphoid neoplasia.}, number={1}, journal={Veterinary and Comparative Oncology}, publisher={Wiley}, author={Seiser, E. L. and Thomas, R. and Richards, K. L. and Kathryn Kelley, M. and Moore, P. and Suter, S. E. and Breen, M.}, year={2011}, month={Nov}, pages={30–50} }
 @article{thomas_seiser_motsinger-reif_borst_valli_kelley_suter_argyle_burgess_bell_et al._2011, title={Refining tumor-associated aneuploidy through ‘genomic recoding’ of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas}, volume={52}, ISSN={1042-8194 1029-2403}, url={http://dx.doi.org/10.3109/10428194.2011.559802}, DOI={10.3109/10428194.2011.559802}, abstractNote={Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. ‘Genomic recoding’ of canine NHL data into a ‘virtual human’ chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.}, number={7}, journal={Leukemia & Lymphoma}, publisher={Informa UK Limited}, author={Thomas, Rachael and Seiser, Eric L. and Motsinger-Reif, Alison and Borst, Luke and Valli, Victor E. and Kelley, Kathryn and Suter, Steven E. and Argyle, David and Burgess, Kristine and Bell, Jerold and et al.}, year={2011}, month={Mar}, pages={1321–1335} }
 @article{mccleary-wheeler_williams_hess_suter_2010, title={Evaluation of an in vitro telomeric repeat amplification protocol assay to detect telomerase activity in canine urine}, volume={71}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.71.12.1468}, DOI={10.2460/ajvr.71.12.1468}, abstractNote={Abstract
Objective—To evaluate the usefulness of a PCR-based telomeric repeat amplification protocol (TRAP) assay for detecting telomerase activity in cells from a canine transitional cell carcinoma (TCC) cell line and, ultimately, in the urine of dogs with TCC.
Animals—11 dogs with histologic or cytologic evidence of TCC, 10 dogs with benign lower urinary tract disease, and 9 healthy dogs.
Procedures—Telomerase activity was initially evaluated in cells from canine TCC (K9TCC) and telomerase-negative (WI-38) cell lines. Following assay optimization, telomerase stability was evaluated at various storage durations and temperatures. Urine samples were then obtained prospectively from study dogs.
Results—Telomerase activity was detected in the K9TCC cell line. The TRAP assay detected telomerase activity in as few as 10 K9TCC cells alone and as low as 2% of a total cell population in K9TCC and WI-38 mixing experiments. A loss of telomerase activity was detected with increasing urine storage durations at various temperatures. Telomerase activity was clearly detected in samples collected from 10 of 11 dogs with TCC, 2 of 10 dogs with benign lower urinary tract disease, and none of the 9 healthy dogs.
Conclusions and Clinical Relevance—The TRAP-based assay detected telomerase activity in the canine TCC cell line and revealed that the telomerase ribonucleoprotein complex was inherently unstable at various storage durations and conditions. Telomerase activity was also detectable in urine samples obtained from dogs with TCC, which suggested the TRAP assay may be useful in diagnosing TCC in dogs.}, number={12}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={McCleary-Wheeler, Angela L. and Williams, Laurel E. and Hess, Paul R. and Suter, Steven E.}, year={2010}, month={Dec}, pages={1468–1474} }
 @article{bizikova_linder_suter_van wettere_olivry_2009, title={Canine cutaneous epitheliotropic T-cell lymphoma with vesiculobullous lesions resembling human bullous mycosis fungoides}, volume={20}, ISSN={0959-4493 1365-3164}, url={http://dx.doi.org/10.1111/j.1365-3164.2009.00760.x}, DOI={10.1111/j.1365-3164.2009.00760.x}, abstractNote={AbstractThe broad spectrum of clinical signs in canine cutaneous epitheliotropic T‐cell lymphoma mimics many inflammatory skin diseases and is a diagnostic challenge. A 13‐year‐old‐male castrated golden retriever crossbred dog presented with multifocal flaccid bullae evolving into deep erosions. A shearing force applied to the skin at the periphery of the erosions caused the epidermis to further slide off the dermis suggesting intraepidermal or subepidermal separation. Systemic signs consisted of profound weight loss and marked respiratory distress. Histologically, the superficial and deep dermis were infiltrated by large, CD3‐positive neoplastic lymphocytes and mild epitheliotropism involved the deep epidermis, hair follicle walls and epitrichial sweat glands. There was partial loss of the stratum basale. Bullous lesions consisted of large dermoepidermal and intraepidermal clefts that contained loose accumulations of neutrophils mixed with fewer neoplastic cells in proteinaceous fluid. The lifted epidermis was often devitalized and bordered by hydropic degeneration and partial epidermal collapse. Similar neoplastic lymphocytes formed small masses in the lungs associated with broncho‐invasion. Clonal rearrangement analysis of antigen receptor genes in samples from skin and lung lesions using primers specific for canine T‐cell receptor gamma (TCRγ) produced a single‐sized amplicon of identical sequence, indicating that both lesions resulted from the expansion of the same neoplastic T‐cell population. Macroscopic vesiculobullous lesions with devitalization of the lesional epidermis should be included in the broad spectrum of clinical signs presented by canine cutaneous epitheliotropic T‐cell lymphoma.}, number={4}, journal={Veterinary Dermatology}, publisher={Wiley}, author={Bizikova, Petra and Linder, Keith E. and Suter, Steven E. and Van Wettere, Arnaud J. and Olivry, Thierry}, year={2009}, month={Aug}, pages={281–288} }
 @article{lurie_gordon_théon_rodriguez_suter_kent_2009, title={Sequential Low-Dose Rate Half-Body Irradiation and Chemotherapy for the Treatment of Canine Multicentric Lymphoma}, volume={23}, ISSN={0891-6640 1939-1676}, url={http://dx.doi.org/10.1111/j.1939-1676.2009.0353.x}, DOI={10.1111/j.1939-1676.2009.0353.x}, abstractNote={Background:  Sequential half‐body irradiation (HBI) combined with chemotherapy is feasible in treating canine lymphoma, but prolonged interradiation intervals may affect efficacy. A 2‐week interradiation interval is possible in most dogs receiving low‐dose rate irradiation (LDRI) protocols at 6 Gy dose levels.Hypothesis:  LDRI incorporated into a cyclophosphamide, doxorubicin, vincritine, and prednisone (CHOP)‐based chemotherapy protocol is effective for the treatment of lymphoma in dogs.Animals:  Thirty‐eight client‐owned animals diagnosed with multicentric lymphoma.Methods:  Retrospective study evaluating the efficacy and prognostic factors for the treatment of canine lymphoma with sequential HBI and chemotherapy.Results:  The median 1st remission was 410 days (95% confidence interval [CI] 241–803 days). The 1‐, 2‐, and 3‐year 1st remission rates were 54, 42, and 31%. The median overall survival was 684 days (95% CI 334–1,223 days). The 1‐, 2‐, and 3‐year survival rates were 66, 47, and 44%.Conclusions and Clinical Relevance:  Results of this study suggest that treatment intensification by a 2‐week interradiation treatment interval coupled with interradiation chemotherapy is an effective treatment for dogs with lymphoma.}, number={5}, journal={Journal of Veterinary Internal Medicine}, publisher={Wiley}, author={Lurie, D.M. and Gordon, I.K. and Théon, A.P. and Rodriguez, C.O. and Suter, S.E. and Kent, M.S.}, year={2009}, month={Sep}, pages={1064–1070} }
 @article{van wettere_linder_suter_olby_2009, title={Solitary Intracerebral Plasmacytoma in a Dog: Microscopic, Immunohistochemical, and Molecular Features}, volume={46}, ISSN={0300-9858 1544-2217}, url={http://dx.doi.org/10.1354/vp.08-VP-0012-V-BC}, DOI={10.1354/vp.08-VP-0012-V-BC}, abstractNote={ A primary intracerebral plasmacytoma was identified in a 7-year-old spayed female Boston Terrier. Grossly, a well-demarcated, 2 cm in diameter, roughly spherical tumor was in the rostral aspect of the left cerebral hemisphere. Histologically, the neoplasm was composed of sheets of round cells with distinct plasmacytoid features and marked anisocytosis and anisokaryosis. Cells were positive for vimentin, CD18, CD79a, and lambda light-chain, and negative for kappa light chain, cytokeratin, lysozyme, glial fibrillary acidic protein, and S100 protein. Clonally rearranged B-cell antigen receptor genes were detected by PARR (polymerase chain reaction for antigen receptor rearrangements), confirming clonal proliferation of B lymphocytes. Although primary solitary intracerebral plasmacytoma is rare in dogs and other species, it should be included in the differential diagnosis for central nervous system round-cell neoplasms. Clonality testing can be utilized to support the histological diagnosis of this neoplasm type. }, number={5}, journal={Veterinary Pathology}, publisher={SAGE Publications}, author={Van Wettere, A. J. and Linder, K. E. and Suter, S. E. and Olby, N. J.}, year={2009}, month={May}, pages={949–951} }
 @article{jamadar-shroff_papich_suter_2009, title={Soy-Derived Isoflavones Inhibit the Growth of Canine Lymphoid Cell Lines}, volume={15}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.CCR-08-1610}, abstractNote={AbstractPurpose: This study aimed to evaluate the in vitro effects of genistein, both pure genistein and a commercially available form of genistein called Genistein Combined Polysacharride (GCP), against two canine B-cell lymphoid cell lines and determine the oral bioavailability of GCP when fed to normal dogs.Experimental Design: The in vitro effect of genistein and GCP was evaluated using cell proliferation and apoptotic assays. The IC50 of both compounds was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay and propidium idodide staining. Apoptosis was evaluated using Annexin V staining, caspase 3 and 9 staining, and DNA laddering. Cell cycle analysis and Bcl-2/Bax ratios were also examined. An initial dose escalating pharmacokinetic study was used to determine if therapeutic serum levels of genistein could be reached with oral dosing of GCP in normal dogs.Results: The 72-hour in vitro IC50 of genistein and GCP against the GL-1 and 17-71 cells were both 10 μg/mL and 20 μg/mL, respectively. GCP led to cell death in both cell lines via apoptosis and treated cells exhibited increased Bax:Bcl-2 ratios. The serum concentrations of genistein in normal dogs given increasing oral doses of GCP did not reach the 72-hour in vitro IC50 in a dose escalation study.Conclusions: The results of these studies support the notion that canine high-grade B-cell lymphoma may represent a relevant large animal model of human non-Hodgkin's lymphoma to investigate the utility of GCP in chemopreventive and/or treatment strategies that may serve as a prelude to human clinical lymphoma trials.}, number={4}, journal={CLINICAL CANCER RESEARCH}, author={Jamadar-Shroff, Vahbiz and Papich, Mark G. and Suter, Steven E.}, year={2009}, month={Feb}, pages={1269–1276} }
 @article{carter_tarigo_vernau_cecere_hovis_suter_2008, title={Erythrophagocytic low-grade extranodal T-cell lymphoma in a cat}, volume={37}, ISSN={0275-6382 1939-165X}, url={http://dx.doi.org/10.1111/j.1939-165X.2008.00073.x}, DOI={10.1111/j.1939-165X.2008.00073.x}, abstractNote={Abstract:  A 13‐year‐old male castrated domestic shorthair cat was presented to the referring veterinarian with a 2‐month history of weight loss and lethargy. Splenomegaly, hepatomegaly, nonregenerative anemia, neutropenia, and hyperbilirubinemia were noted. Results of testing for feline immunodeficiency virus, feline leukemia virus, Toxoplasma gondii, and Mycoplasma sp. were negative. On cytologic examination of aspirates from the enlarged spleen and liver, a population of erythrophagocytic round cells was observed. Splenectomy and a liver biopsy were done which revealed a population of CD3+/CD79a– erythrophagocytic mononuclear round cells localized in the hepatic and splenic sinusoids. T‐cell PARR (PCR for antigen receptor gene rearrangements) analysis of bone marrow and spleen demonstrated a single band indicative of a clonal proliferation of T cells. Based on the marked splenomegaly, sinusoidal infiltration, lack of lymphadenopathy, and results of cytology, PARR, and immunophenotyping, a diagnosis of low‐grade extranodal T‐cell lymphoma was made. The cat was treated with chlorambucil and prednisolone; clinical and laboratory abnormalities resolved and the cat has remained clinically normal for 2.5 years. To our knowledge, this report documents the first case of an erythrophagocytic T‐cell lymphoma in a cat. The clinicopathologic findings were suggestive of hepatosplenic T‐cell lymphoma, a neoplasm described previously only in humans and dogs.}, number={4}, journal={Veterinary Clinical Pathology}, publisher={Wiley}, author={Carter, J. E. and Tarigo, J. L. and Vernau, W. and Cecere, T. E. and Hovis, R. L. and Suter, S. E.}, year={2008}, month={Dec}, pages={416–421} }
 @article{lurie_milner_suter_vernau_2008, title={Immunophenotypic and cytomorphologic subclassification of T-cell lymphoma in the boxer breed}, volume={125}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2008.05.009}, abstractNote={The boxer breed is at high risk for developing lymphoma and, in contrast to the general canine population, is predisposed to the T-cell variant of the disease. The purpose of this study was to more accurately classify lymphoma in this breed. Clinical, cytomorphologic and immunophenotypic data were examined in 43 boxers with lymphoma. Twenty-five cases were collected prospectively and a further 18 cases were obtained retrospectively. Lymphomas were classified as multicentric (n=29), mediastinal (n=6) and intestinal (n=8). Of the 40 immunophenotyped samples, 34 (85%) were T-cell, 5 (12.5%) were B-cell and 1 was a non-B-cell non-T-cell lymphoma. Immunophenotypic subtyping was done on prospectively collected T-cell lymphoma samples (n=22) to differentiate CD4 (helper) from CD8 (cytotoxic) T-cell origin as well as to determine the T-cell receptor (TCR) expression (TCRalphabeta vs. TCRdeltagamma). Phenotypic expression was CD4+ (n=12), double negative (DN) (n=6), double positive (DP) (n=1) and CD8+ (n=1), respectively, while two samples had no interpretable result. 20/22 samples were TCRalphabeta+ with only 1 sample being TCRdeltagamma+ and 1 with no interpretable result. Cytomorphologic analysis was done on the same 22 samples using the World Health Organization (WHO) classification scheme. According to this scheme, 17/22 samples were classified as lymphoblastic, 2/22 as large cell peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), 2/22 as large granular lymphoma (LGL) high-grade and 1/22 as small lymphocytic. The results of this study indicate that lymphoma in the boxer breed is a disease comprised predominantly of TCRalphabeta+, CD4+ (helper) T-cells with lymphoblastic (high-grade) morphology.}, number={1-2}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Lurie, David M. and Milner, Rowan J. and Suter, Steven E. and Vernau, William}, year={2008}, month={Sep}, pages={102–110} }
 @article{suter_vernau_fry_london_2007, title={CD34(+), CD41(+) acute megakaryoblastic leukemia in a dog}, volume={36}, ISSN={["0275-6382"]}, DOI={10.1111/j.1939-165X.2007.tb00227.x}, abstractNote={AbstractA clinically normal, 5‐year‐old intact female German Shepherd dog was presented to the local veterinarian to be spayed. Results of a preoperative CBC included mild nonregenerative anemia, severe thrombocytopenia, and 17% unclassified cells. On cytologic examination of aspirates from the dog's enlarged spleen and peripheral lymph nodes, a population of primitive round cells that occasionally resembled megakaryocytes was observed. A bone marrow aspirate specimen was markedly hypercellular with approximately 65% of marrow cells comprising a homogeneous population of immature hematopoietic cells similar to those found in the spleen, lymph nodes, and peripheral blood. Using immunocytochemical stains with canine‐specific antibodies, all neoplastic cells strongly expressed cytoplasmic CD41 and 20–70% of the neoplastic cells expressed CD34 weakly to moderately. Rare (<0.5%) neoplastic cells weakly expressed vWF. The cells were negative for all other markers. Based on these results and the morphology of the neoplastic cells, a diagnosis of acute megakaryoblastic leukemia (AMegL) was made. In spite of treatment, results of a CBC performed 1 week later indicated progressive anemia and thrombocytopenia, and the dog was euthanized. To our knowledge, this report documents the first case of canine AMegL diagnosed with both anti‐canine CD34 and CD41 antibodies.}, number={3}, journal={VETERINARY CLINICAL PATHOLOGY}, author={Suter, Steven E. and Vernau, William and Fry, Michael M. and London, Cheryl A.}, year={2007}, month={Sep}, pages={288–292} }
 @article{suter_gouthro_o'malley_hartnett_mcsweeney_moore_felsburg_haskins_henthorn_2007, title={Marking of peripheral T-lymphocytes by retroviral transduction and transplantation of CD34(+) cells in a canine X-linked severe combined immunodeficiency model}, volume={117}, ISSN={["0165-2427"]}, DOI={10.1016/j.vetimm.2007.03.004}, abstractNote={A retrovirus vector containing an enhanced green fluorescent protein complimentary DNA (EGFP cDNA) was used to mark and dynamically follow vector-expressing cells in the peripheral blood of bone marrow transplanted X-linked severe combined immunodeficient dogs. CD34(+) cells isolated from young normal dogs were transduced, using a 2 day protocol, with an amphotropic retroviral vector that expressed enhanced green fluorescent protein (EGFP) and the canine common gamma chain (gammac) cDNAs. Following transplantation of the transduced cells, normal donor peripheral blood lymphocytes (PBL) appeared by 1 month post-bone marrow transplant (BMT) and rescued three of five treated dogs from their lethal immunodeficiency. PCR and flow cytometric analysis of post-BMT PBL documented the peripheral EGFP expressing cells as CD3(+) T cells, which varied from 0% to 28%. Sorting of EGFP(+) and EGFP(-) peripheral blood T cells from two dogs, followed by vector PCR analysis, showed no evidence of vector shutdown. EGFP expression in B cells or monocytes was not detected. These marking experiments demonstrate that the transduction protocol did not abolish the lymphoid engraftment capability of ex vivo transduced canine CD34(+) cells and supports the potential utility of the MSCV retroviral vector for gene transfer to XSCID affected canine hematopoietic progenitor cells (HPC).}, number={3-4}, journal={VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY}, author={Suter, Steven E. and Gouthro, Terry A. and O'Malley, Thomas and Hartnett, Brian J. and McSweeney, Peter A. and Moore, Peter F. and Felsburg, Peter J. and Haskins, Mark E. and Henthorn, Paula S.}, year={2007}, month={Jun}, pages={183–196} }
 @article{weeth_fascetti_kass_suter_santos_delaney_2007, title={Prevalence of obese dogs in a population of dogs with cancer}, volume={68}, ISSN={0002-9645}, url={http://dx.doi.org/10.2460/ajvr.68.4.389}, DOI={10.2460/ajvr.68.4.389}, abstractNote={Abstract
Objective—To determine the body condition score (BCS) distribution for dogs examined at a teaching hospital and examine whether the BCS distribution for dogs with cancer differed significantly from the distribution for dogs without cancer.
Sample Population—1,777 dogs with cancer and 12,893 dogs without cancer.
Procedures—A retrospective prevalence case-control study was conducted that used medical records from 1999 to 2004. Information was collected on BCS (9-point system), age, breed, sex, neuter status, diagnosis, and corticosteroid administration. Body condition score at the time of examination for cancer (dogs with cancer) or first chronologic visit (dogs without cancer) was recorded. Logistic regression was used to compare BCS prevalence distributions between groups.
Results—The overall prevalence of obese dogs (BCS ≥ 7/9) was 14.8% (2,169/14,670), and the overall prevalence of overweight dogs (BCS ≥ 6/9 to < 7/9) was 21.6% (3,174/14,670). There was a significant difference in the BCS distribution between dogs with and without cancer, with a slightly lower prevalence of being overweight and obese in dogs with cancer. The prevalence of obese and overweight dogs varied with specific cancer types when compared with the prevalence for dogs without cancer.
Conclusions and Clinical Relevance—Differences in obesity prevalence among cancer types is suggestive of an incongruous effect of this variable on cancer expression or a differential effect of specific cancer types on weight status. Systematic use of BCSs will help elucidate the association between obesity and cancer development.}, number={4}, journal={American Journal of Veterinary Research}, publisher={American Veterinary Medical Association (AVMA)}, author={Weeth, Lisa P. and Fascetti, Andrea J. and Kass, Philip H. and Suter, Steven E. and Santos, Aniel M. and Delaney, Sean J.}, year={2007}, month={Apr}, pages={389–398} }
 @article{suter_gouthro_mcsweeney_nash_haskins_felsburg_henthorn_2006, title={Optimized Transduction of Canine Paediatric CD34+ Cells Using an MSCV-based Bicistronic Vector}, volume={30}, ISSN={0165-7380 1573-7446}, url={http://dx.doi.org/10.1007/s11259-006-3356-7}, DOI={10.1007/s11259-006-3356-7}, abstractNote={We have used a murine MSCV-based bicistronic retroviral vector, containing the common gamma chain (gammac) and enhanced green fluorescent protein (EGFP) cDNAs, to optimize retroviral transduction of canine cells, including an adherent canine thymus fibroblast cell line, Cf2Th, as well as normal canine CD34(+) bone marrow (BM) cells. Both canine cell types were shown to express Ram-1 (the amphotropic retroviral receptor) mRNA. Supernatants containing infectious viruses were produced using both stable (PA317) and transient (Phoenix cells) amphotropic virus producer cell lines. Centrifugation (spinfection) combined with the addition of polybrene produced the highest transduction efficiencies, infecting approximately 75% of Cf2Th cells. An average of 11% of highly enriched canine CD34(+) cells could be transduced in a protocol that utilized spinfection and plates coated with the fibronectin fragment CH-296 (Retronectin). Indirect assays showed the vector-encoded canine gammac cDNA produced a gammac protein that was expressed on the cell surface of transduced cells. This strategy may result in the transduction of sufficient numbers of CD34(+) BM cells to make the treatment of canine X-linked severe combined immunodeficiency and other canine genetic diseases feasible.}, number={8}, journal={Veterinary Research Communications}, publisher={Springer Science and Business Media LLC}, author={Suter, S. E. and Gouthro, T. A. and McSweeney, P. A. and Nash, R. A. and Haskins, M. E. and Felsburg, P. J. and Henthorn, P. S.}, year={2006}, month={Nov}, pages={881–901} }
 @article{henson_suter_von messling_cattaneo_fielding_2005, title={803. The Effects of Intratumoral Injection of a Replicating Morbillivirus in a Canine Model of Naturally Occurring Lymphoma}, volume={11}, ISSN={1525-0016}, url={http://dx.doi.org/10.1016/j.ymthe.2005.07.340}, DOI={10.1016/j.ymthe.2005.07.340}, abstractNote={Many viruses have a greater capacity to replicate within and lyse transformed cells than in normal cells. Those replicating oncolytic viruses with low pathogenicity in humans are receiving increasing attention as potential therapies for cancer. We previously established that the non-pathogenic, vaccine strain of measles virus (MV) could cause regression of established lymphoma xenografts in mice. However, murine models have considerable limitations in predicting response in humans; this is particularly true in the case of studies with MV in particular, since MV does not infect murine cells.}, number={Supplement 1}, journal={Molecular Therapy}, publisher={Elsevier BV}, author={Henson, Michael S. and Suter, Steven E. and von Messling, Veronika A. and Cattaneo, Roberto and Fielding, Adele K.}, year={2005}, month={May}, pages={S312} }
 @article{suter_2005, title={In vitro Canine Distemper Virus Infection of Canine Lymphoid Cells: A Prelude to Oncolytic Therapy for Lymphoma}, volume={11}, ISSN={1078-0432 1557-3265}, url={http://dx.doi.org/10.1158/1078-0432.ccr-04-1944}, DOI={10.1158/1078-0432.ccr-04-1944}, abstractNote={AbstractPurpose: Measles virus (MV) causes the regression of human lymphoma xenografts. The purpose of this study was to determine if canine lymphoid cells could be infected in vitro with MV or canine distemper virus (CDV, the canine Morbillivirus equivalent of MV) and determine if in vitro viral infection leads to apoptotic cell death.Experimental Design: Reverse transcriptase-PCR was used to examine the expression of both signal lymphocyte activation molecule (CD150) and membrane cofactor molecule (CD46) mRNA. An attenuated CDV expressing enhanced green fluorescent protein was used to infect canine cells in vitro. Both flow cytometry and reverse transcriptase-PCR was used to document CDV infection. Cell death was examined using a propidium iodide staining assay and Annexin V binding.Results: Canine lymphoid cell lines and neoplastic B and T lymphocytes collected from dogs with spontaneous lymphoma expressed the Morbillivirus receptor CD150 mRNA. In contrast, only neoplastic lymphocytes expressed detectable levels of CD46 mRNA. Although MV did not infect canine cells, CDV efficiently infected between 40% and 70% of all three canine lymphoid lines tested. More importantly, CDV infected 50% to 90% of neoplastic lymphocytes isolated from dogs with both B and T cell lymphoma. Apoptosis of CDV-infected cell lines was documented.Conclusions: Attenuated CDV may be a useful treatment for canine lymphoma. As such, dogs with lymphoma may represent a biologically relevant large animal model to investigate the feasibility, safety, and efficacy of Morbillivirus therapy in a clinical setting with findings that may have direct applicability in the treatment of human non-Hodgkin's lymphoma.}, number={4}, journal={Clinical Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Suter, S. E.}, year={2005}, month={Feb}, pages={1579–1587} }
 @article{suter_gouthro_mcsweeney_nash_haskins_felsburg_henthorn_2004, title={Isolation and characterization of pediatric canine bone marrow CD34+ cells}, volume={101}, ISSN={0165-2427}, url={http://dx.doi.org/10.1016/j.vetimm.2004.03.009}, DOI={10.1016/j.vetimm.2004.03.009}, abstractNote={Historically, the dog has been a valuable model for bone marrow transplantation studies, with many of the advances achieved in the dog being directly transferable to human clinical bone marrow transplantation protocols. In addition, dogs are also a source of many well-characterized homologues of human genetic diseases, making them an ideal large animal model in which to evaluate gene therapy protocols. It is generally accepted that progenitor cells for many human hematopoietic cell lineages reside in the CD34+ fraction of cells from bone marrow, cord blood, or peripheral blood. In addition, CD34+ cells are the current targets for human gene therapy of diseases involving the hematopoietic system. In this study, we have isolated and characterized highly enriched populations of canine CD34+ cells isolated from dogs 1 week to 3 months of age. Bone marrow isolated from 2- to 3-week-old dogs contained up to 18% CD34+ cells and this high percentage dropped sharply with age. In in vitro 6-day liquid suspension cultures, CD34+ cells harvested from 3-week-old dogs expanded almost two times more than those from 3-month-old dogs and the cells from younger dogs were also more responsive to human Flt-3 ligand (Flt3L). In culture, the percent and number of CD34+ cells from both ages of dogs dropped sharply between 2 and 4 days, although the number of CD34+ cells at day 6 of culture was higher for cells harvested from the younger dogs. CD34+ cells harvested from both ages of dogs had similar enrichment and depletion values in CFU-GM methylcellulose assays. Canine CD34+/Rho123lo cells expressed c-kit mRNA while the CD34+/Rhohi cells did not. When transplanted to a sub-lethally irradiated recipient, CD34+ cells from 1- to 3-week-old dogs gave rise to both myeloid and lymphoid lineages in the periphery. This study demonstrates that canine CD34+ bone marrow cells have similar in vitro and in vivo characteristics as human CD34+ cells. In addition, ontogeny-related functional differences reported for human CD34+ cells appear to exist in the dog as well, suggesting pediatric CD34+ cells may be better targets for gene transfer than adult bone marrow. The demonstration of similarities between canine and human CD34+ cells enhances the dog as a large, preclinical model to evaluate strategies for improving bone marrow transplantation protocols, for gene therapy protocols that target CD34+ cells, and to study the engraftment potential of various cell populations that may contain hematopoietic progenitor cell activity.}, number={1-2}, journal={Veterinary Immunology and Immunopathology}, publisher={Elsevier BV}, author={Suter, Steven E. and Gouthro, Terry A. and McSweeney, Peter A. and Nash, Richard A. and Haskins, Mark E. and Felsburg, Peter J. and Henthorn, Paula S.}, year={2004}, month={Sep}, pages={31–47} }
 @article{hartnett_yao_suter_ellinwood_henthorn_moore_mcsweeney_nash_brown_weinberg_et al._2002, title={Transplantation of X-linked severe combined immunodeficient dogs with CD34+ bone marrow cells}, volume={8}, ISSN={1083-8791}, url={http://dx.doi.org/10.1053/bbmt.2002.v8.pm12014808}, DOI={10.1053/bbmt.2002.v8.pm12014808}, abstractNote={X-linked severe combined immunodeficiency (X-SCID) is the most common form of human SCID and is caused by mutations in the common gamma chain (gammac), a shared component of the interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 receptors. BMT for human X-SCID results in engraftment of donor T-cells and reconstitution of normal T-cell function but engraftment of few, if any, donor B-cells and poor reconstitution of humoral immune function. Canine X-SCID is also caused by mutations in the yc and has an immunological phenotype identical to that of human X-SCID. We have previously reported that transplantation of nonconditioned X-SCID dogs with unfractionated histocompatible bone marrow results in engraftment of both donor B- and T-cells and reconstitution of normal T-cell and humoral immune function. In this study, we assessed the ability of purified canine CD34+ bone marrow cells to reconstitute lymphoid populations after histocompatible BMT in 6 nonablated X-SCID dogs. All dogs showed engraftment of donor T-cells, with T-cell regeneration occurring through a thymic-dependent pathway, and had reconstituted normal T-cell function. In contrast to our previous studies, only 3 dogs had engraftment of donor B-cells and reconstituted normal antigen-specific B-cell function post-BMT. The variable donor B-cell engraftment and reconstitution of normal humoral immune function observed in this study are similar to the outcomes observed in the majority of human X-SCID patients following BMT. This study demonstrates that canine CD34+ cells contain progenitors capable of immune reconstitution and is the first study to document the ability of CD34+ bone marrow cells to reconstitute normal B- and T-cell function in a nonablated large-animal model of BMT. This study also demonstrates that the quality of immune reconstitution following CD34+ BMT may be dosage dependent Thus canine X-SCID provides a large-animal preclinical model that can be used not only to determine the optimal conditions for both donor B- and T-cell engraftment following CD34 BMT, but also to develop and evaluate strategies for gene therapy protocols that target CD34 cells.}, number={4}, journal={Biology of Blood and Marrow Transplantation}, publisher={Elsevier BV}, author={Hartnett, Brian J and Yao, DaPeng and Suter, Steven E and Ellinwood, N.Matthew and Henthorn, Paula S and Moore, Peter F and McSweeney, Peter A and Nash, Richard A and Brown, Jeffrey D and Weinberg, Kenneth I and et al.}, year={2002}, month={Apr}, pages={188–197} }
 @article{hartnett_suter_henthorn_weinberg_moore_ochs_felsburg_1997, title={Bone Marrow Transplantation (BMT) of X-SCID dogs with d c chain heterozygous bone marrow cells}, volume={V0099}, number={414}, journal={Journal of Allergy and Clinical Immunology}, author={Hartnett, B.J. and Suter, S.E. and Henthorn, P.E. and Weinberg, K.I. and Moore, P.F. and Ochs, H.D. and Felsburg, P.J.}, year={1997}, pages={255} }
 @article{felsburg_somberg_hartnett_suter_henthorn_moore_weinberg_ochs_1997, title={Full immunological reconstitution following non-conditional bone marrow transplantation for canine X-linked secure combined immunodeficiency}, volume={90}, journal={Blood}, author={Felsburg, P.F. and Somberg, R.L. and Hartnett, B.J. and Suter, S.E. and Henthorn, P.S. and Moore, P.F. and Weinberg, K.I. and Ochs, H.P.}, year={1997}, pages={3212–3221} }