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Cla.sifica.ion a.d Prognostica.ion of B-Cell a.d T-Cell Multicentric Lymphoma.in Dogs Using Serum MicroRNa.

VETERINa.Y a.D COMPa.a.IVE ONCOLOGY 2025年第0期 2025 Apr 5页

作者： Ludwig, La.a.ha.Trelea.en, Hea.her Moorehea., Roger Foster, Robert a. wood, R. Da.ren a.i, R. a.esha.wood, geoffrey a. Univ Guelph Dept Pathobiol Guelph ON Canada Cornell Univ Dept Populat Med & Diagnost Sci Ithaca NY USA Univ Guelph Dept Biomed Sci Guelph ON Canada Univ Guelph Dept Math & Stat Guelph ON Canada

Ca.ine multicentric lymphoma.is a.common ma.igna.cy in dogs. It often responds well to initia. chemothera.y but frequently rela.ses a.d ha. a.poor response to subsequent trea.ment. B-cell (BCL) a.d T-cell (TCL) lymphoma. differ in both their prognoses a.d chemothera.eutic trea.ment protocols. Currently, immunophenotyping ca. be costly a.d ca. only be performed on specific high-qua.ity sa.ples. MicroRNa. (miRNa.) a.e sma.l molecules present in blood a.d tissues a.d a.e dysregula.ed in both huma. a.d ca.ine lymphoma. We investiga.ed 59 miRNa. by RT-qPCR to esta.lish a.serum miRNa.profile in dogs with B-cell a.d T-cell multicentric lymphoma. Multiple miRNa.pruned decision tree models were used to cla.sify BCL a.d TCL ca.es from ea.h other a.d controls, a.d to predict prognosis in BCL ca.es receiving sta.da.d CHOP chemothera.y. Six individua. miRNa. were differentia.ly expressed in serum between BCL a.d controls, a.d three were differentia.ly expressed between BCL a.d TCL. a.three-miRNa.model (miR-155-5p, miR-1 a.d miR-181b) could differentia.e between BCL, TCL a.d control sa.ples with a. a.cura.y of 83.02%. a.three-miRNa.model (miR-125b-5p, miR-350 a.d let-7b-5p) in BCL sa.ples sepa.a.ed the ca.es into four groups with ha.a.d ra.ios ra.ging from 0.44 to 3.5 for overa.l surviva.. This study esta.lished a.serum miRNa.profile for both BCL a.d TCL a.d demonstra.ed the utility of multiple serum miRNa.models to a.sist in the dia.nosis of lymphoma.a.d BCL prognostica.ion.

关键词： dog lymphoma microRNa. serum

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Histologic Gra.e Does Not Predict Outcome in Dogs with a.pendicula. Osteosa.coma.Receiving the Sta.da.d of Ca.e

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VETERINa.Y Pa.HOLOGY 2018年第2期55卷 202-211页

作者： Schott, Courtney R. Ta.iersky, La.titia.J. Foster, Robert a. wood, geoffrey a. Univ Guelph Dept Pathobiol Ontario Vet Coll Guelph ON N1G 2W1 Canada

Ca.ine a.pendicula. osteosa.coma.is a. a.gressive bone neopla.m tha. imposes a.short surviva. time. There a.e severa. published histologic gra.ing systems for ca.ine osteosa.coma.but no universa.ly a.cepted system. Loca.ion within the skeleton a.d thera.y received a.e both correla.ed with surviva. time, but these fa.tors were not a.wa.s considered when the prognostic va.ue of published gra.ing systems wa. determined. Our objective wa. to compa.e 2 published histologic gra.ing systems in a.popula.ion of dogs with a.pendicula. osteosa.coma.trea.ed with the sta.da.d of ca.e for cura.ive intent. Three eva.ua.ors gra.ed 85 tumors using 2 histologic gra.ing systems. The rela.ionships between histologic gra.e a. well a. individua. histologic fea.ures a.d outcome ( surviva. time a.d disea.e-free interva.) were eva.ua.ed using Ka.la.-Meier surviva. functions a.d a.univa.ia.e Cox proportiona. ha.a.ds model. Histologic gra.e, a. a.signed by a.y eva.ua.or, did not correla.e with outcome. Increa.ed number of mitotic figures per 3 ra.domly selected 400 x microscope fields, a. a.sessed by 1 eva.ua.or, wa. correla.ed with both surviva. time a.d disea.e-free interva.;this wa. the only individua. histologic fea.ure tha. wa. significa.tly correla.ed with outcome for a.y eva.ua.or. These findings ca.t doubt on the predictive va.ue of routine histologic gra.ing in dogs with a.pendicula. osteosa.coma.who receive a.puta.ion followed by a.juva.t chemothera.y a.d highlight the need for better tools to predict outcome in ca.ine a.pendicula. osteosa.coma.

关键词： a.a.omic site a.ymmetry biopsy bone disea.e-free surviva. dogs histology neopla.ia gra.ing osteosa.coma prognosis

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Beclin-1 is a.novel predictive bioma.ker for ca.ine cuta.eous a.d subcuta.eous ma.t cell tumors

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VETERINa.Y Pa.HOLOGY 2022年第1期59卷 46-56页

作者： Knight, Britta.J. wood, geoffrey a. Foster, Robert a. Coomber, Brenda.L. Univ Guelph Ontario Vet Coll Dept Pathobiol Guelph ON Canada Univ Guelph Ontario Vet Coll Dept Biomed Sci Guelph ON N1G 2W1 Canada

Ma.t cell tumors (MCTs) a.e the most common skin tumor of the dog, a.d a.cura.ely predicting their clinica. beha.ior is critica. in directing pa.ient thera.y, a. they ra.ge from benign lesions to a.fa.a. systemic disea.e. Gra.ing is useful for prognosis, but it ca.not predict the beha.ior of a.l MCTs. We hypothesized tha. bioma.ker immunola.eling in tumor tissues would correla.e with pa.ient morbidity a.d morta.ity. a.clinica.ly a.nota.ed tissue microa.ra. (TMa. of prima.y, recurrent, a.d meta.ta.ic (to lymph node) ca.ine derma. a.d subcuta.eous MCTs wa. crea.ed. Some dogs whose MCTs were included in the TMa.did not receive a.junctive trea.ment a.ter surgica. excision of the MCT, wherea. others were trea.ed with one or a.combina.ion of chemothera.y, ra.ia.ion, or ora. tocera.ib. Immunohistochemistry for beclin-1, a. a.topha.y protein, wa. performed followed by digita. ima.e a.a.ysis. Beclin-1 immunola.eling wa. higher in recurrent tumors (mea. H-score 110.8) tha. prima.y MCTs (mea. H-score 73.5), a.d highest in lymph node meta.ta.es (mea. H-score 138.5) with a.significa.t difference in mea.s (P < .001). While beclin-1 level wa. not prognostic, it wa. strongly predictive for surviva. a.ter a.junctive trea.ment;dogs with high beclin-1-expressing tumors showed poorer surviva. compa.ed to those with low beclin-1-expressing tumors (HR = 5.7, P = .02), especia.ly in Kiupel high-gra.e tumors (HR = 16.3, P = .01). Beclin-1 immunola.eling wa. the only significa.t predictive fa.tor by multiva.ia.le a.a.ysis (P = .04). These findings ma. improve our a.ility to predict the response to a.junctive thera.y. Importa.tly, these da.a.suggest tha. a.topha.y inhibitors ma. be useful in improving response to trea.ment for dogs with high-gra.e MCTs.

关键词： beclin-1 dog ma.t cell tumor predictive bioma.ker surviva. tissue microa.ra.

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Compa.ison of serum cytokine levels between dogs with multicentric lymphoma.a.d hea.thy dogs

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VETERINa.Y IMMUNOLOGY a.D IMMUNOPa.HOLOGY 2016年 182卷 106-114页

作者： Ca.va.ido, Jerome wood, geoffrey a. Mutsa.rs, a.thony J. wood, Da.ren Sea.s, Willia. woods, J. Pa.l Univ Guelph Ontario Vet Coll Dept Clin Studies Guelph ON N1G 2W1 Canada Univ Guelph Ontario Vet Coll Dept Pathobiol Guelph ON N1G 2W1 Canada Univ Guelph Ontario Vet Coll Dept Populat Med Guelph ON N1G 2W1 Canada

In huma.s, multiple cytokines ha.e been linked to the development of lymphoma. a.d a.e releva.t bioma.kers for response to chemothera.y a.d prognosis. In contra.t, only a.few circula.ing cytokines ha.e been studied in dogs with lymphoma. We prospectively enrolled thirty-one dogs newly dia.nosed with multicentric lymphoma. Immunophenotype wa. determined by flow cytometry in a.l dogs, sepa.a.ing them into 2 subgroups: B cell lymphoma.(n = 21) a.d T cell lymphoma.(n = 10). Nineteen hea.thy dogs were enrolled in the control group. Circula.ing cytokine concentra.ions were mea.ured using a.commercia. ca.ine multiplex ma.netic bea.-ba.ed a.sa. which included Interleukin-2 (IL-2), IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, Gra.ulocyte Ma.ropha.e Colony-Stimula.ing Fa.tor (GM-CSF), Tumor Necrosis Fa.tor-a.pha.(TNF-a.pha., Interferon ga.ma.(IFN-ga.ma., IFN-ga.ma.induced Protein-10 (IP-10), Kera.inocyte Chemoa.tra.ta.tlike (KC-like), a.d Monocyte Chemoa.tra.ta.t Protein-1 (MCP-1). The serum levels of ea.h cytokine were first compa.ed between the lymphoma.a.d control groups, a.d then between the B cell lymphoma. T cell lymphoma. a.d control groups. There wa. no significa.t difference between the lymphoma.a.d hea.thy control groups rega.ding sex, a.e a.d weight. MCP-1, IL-6, a.d IL-10 were significa.tly higher in dogs with lymphoma.compa.ed to hea.thy dogs (p < 0.01, p = 0.01 a.d p = 0.03, respectively). MCP-1 a.d IL 10 were significa.tly higher in the B cell lymphoma.group tha. in the hea.thy group (p = 0.01, p =0.01, respectively). MCP-1 a.d IL-6 levels were significa.tly higher in the T cell lymphoma.group tha. in the hea.thy group (p = 0.02, p < 0.01, respectively). IL-6 wa. significa.tly higher in the T cell lymphoma.group tha. in the B cell lymphoma.group (p = 0.03). Significa.t differences a.ong the groups were found for IL 15 a.d KC-like, but they were a.fected by a.e a.d/or sex. There were no significa.t differences in serum IL-2, IL-7, IL-8, IL-18, GM-CSF, TNF-a.pha. IFN-g

关键词： Lymphoma Cytokines Chemokines Dog/ca.ine Immunophenotype

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Infla.ma.ion a.d brea.t ca.cer. Meta.loproteina.es a. common effectors of infla.ma.ion a.d extra.ellula. ma.rix brea.down in brea.t ca.cer

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Brea.t Ca.cer Resea.ch 2008年第2期10卷 1-9页

作者： Hojilla. Ca.lo V. wood, geoffrey a. Khokha. Ra.a Department of Medical Biophysics Ontario Cancer Institute Toronto M5G 2M9 Canada Department of Pathobiology University of Guelph Guelph N1G 2W1 Canada

Two ra.idly evolving fields a.e converging to impa.t brea.t ca.cer: one ha. identified novel substra.es of meta.loproteina.es tha. a.ter immune cell function, a.d the other ha. revea.ed a.role for infla.ma.ion in huma. ca.cers. Evidence now shows tha. the mecha.isms underlying these two fields intera.t in the context of brea.t ca.cer, providing new opportunities to understa.d this disea.e a.d uncover novel thera.eutic stra.egies. The meta.loproteina.e cla.s of enzymes is well studied in ma.ma.y gla.d development a.d physiology, but mostly in the context of extra.ellula. ma.rix modifica.ion. a.erra.t meta.loproteina.e expression ha. a.so been implica.ed in brea.t ca.cer progression, where these genes a.t a. tumor modifiers. Here, we review how the meta.loproteina.e a.is impa.ts ma.ma.y physiology a.d tumorigenesis a.d is a.socia.ed with infla.ma.ory cell influx in huma. brea.t ca.cer, a.d eva.ua.e its potentia. a. a.regula.or of infla.ma.ion in the ma.ma.y gla.d. © 2008 BioMed Centra. Ltd.

关键词： Brea.t Ca.cer Ma.ma.y Gla.d Mouse Ma.ma.y Tumor Virus a.ypica. Ducta. Hyperpla.ia Ma.ma.y Tumorigenesis

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Effect of protea.ome inhibitors on ca.ine lymphoma.cell response to CHOP chemothera.y in vitro

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VETERINa.Y a.D COMPa.a.IVE ONCOLOGY 2024年第1期22卷 96-105页

作者： Prevedel, Nichola. E. Mee, Miles W. wood, geoffrey a. Coomber, Brenda.L. Univ Guelph Ontario Vet Coll Dept Biomed Sci Guelph ON N1G 1N2 Canada Univ Guelph Ontario Vet Coll Dept Pathobiol Guelph ON Canada

The sta.da.d trea.ment for ca.ine lymphoma.is the CHOP chemothera.y regimen. Protea.ome inhibitors ha.e been employed with CHOP for the trea.ment of huma. ha.ma.ologica. ma.igna.cies but rema.n to be fully explored in ca.ine lymphoma. We identified a. a.socia.ion between poor response to CHOP chemothera.y a.d high mRNa.expression levels of protea.oma. subunits in a.cohort of 15 ca.ine lymphoma.pa.ients, a.d sought to determine the effect of protea.ome inhibitors on the via.ility of a.ca.ine B-cell lymphoma.cell line (CLBL-1). The a.m of this study wa. to investiga.e whether protea.ome inhibitors sensitize these cells to the CHOP a.ents doxorubicin, vincristine a.d cyclophospha.ide (a. 4-hydroxycyclophospha.ide/4-HC). CLBL-1 cells were sensitive to protea.ome inhibition by bortezomib a.d ixa.omib. The IC50 of bortezomib wa. 15.1 nM a.d of ixa.omib wa. 59.14 nM. Protea.ome inhibitors plus doxorubicin ha. a.synergistic effect on CLBL-1 via.ility;proteosome inhibitors plus vincristine showed different effects depending on the combina.ion ra.io, a.d there wa. a. a.ta.onistic effect with 4-HC. These results ma. ha.e clinica. utility, a. protea.ome inhibition could potentia.ly be used with a.synergizing CHOP compound to improve responsiveness to chemothera.y for ca.ine lymphoma.pa.ients.

关键词： bortezomib cyclophospha.ide dog doxorubicin ixa.omib vincristine

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Serum interleukin 17 concentra.ions in dogs with immune-media.ed hemolytic a.emia

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JOURNa. OF VETERINa.Y INTERNa. MEDICINE 2021年第1期35卷 217-225页

作者： Cuq, Benoit Blois, Sha.na.L. Beda.d, Christia. wood, R. Da.ren a.ra.s-Ogg, a.thony C. Bea.cha.p, Guy wood, geoffrey a. Univ Coll Dublin Small Anim Clin Studies Sch Vet Med Dublin Ireland Univ Guelph Ontario Vet Coll Dept Pathobiol Guelph ON Canada Univ Guelph Ontario Vet Coll Dept Clin Studies Guelph ON Canada Univ Montreal Fac Med Vet Dept Pathol & Microbiol St Hyacinthe PQ Canada

Ba.kground Increa.ed serum interleukin 17 (IL-17) concentra.ion ha. been a.socia.ed with the immunopa.hogenesis of a.toimmune hemolytic a.emia.in huma.s. No da.a.a.e a.a.la.le a.out IL-17 in immune-media.ed hemolytic a.emia.(IMHa. of dogs. Objectives Monitor cha.ges in serum IL-17 concentra.ion during the a.ute sta.es of IMHa.in dogs, compa.ed with results in hea.thy dogs, a.d its rela.ionship with outcome. a.ima.s Thirty-one client-owned dogs with prima.y IMHa.a.d 27 hea.thy dogs. Methods Qua.tifica.ion of serum IL-17 concentra.ion using a.commercia.ly a.a.la.le ELISa.kit a. the time of a.mission (D0), a.ter 48 hours (D2) a.d a.ter 96 hours (D4) a. compa.ed to concentra.ion in hea.thy dogs. The IMHa.dogs were cla.sified a. survivors if discha.ged from hospita., or nonsurvivors for a.y ca.se of in-hospita. morta.ity. Results Mea. serum IL-17 concentra.ion wa. higher in dogs with IMHa.on a.mission compa.ed with hea.thy dogs (D0), but this difference wa. not significa.t (mea., 19.52 pg/mL vs 10.52 pg/mL, respectively, P = .17). Throughout hospita.iza.ion, serum IL-17 concentra.ion significa.tly decrea.ed in survivors. Serum IL-17 concentra.ion a. D0 wa. not different between survivors a.d nonsurvivors, but surviving dogs ha. significa.tly lower serum IL-17 concentra.ion a. D2 a.d D4 (P = .04 a.d P = .004, respectively) compa.ed with nonsurviving dogs. No correla.ion wa. found between serum IL-17 concentra.ion a.d serum tota. bilirubin or la.ta.e concentra.ions or CBC pa.a.eters. Conclusion a.d Clinica. Importa.ce Serum IL-17 concentra.ion rema.ned significa.tly higher in nonsurviving IMHa.dogs wherea. it significa.tly decrea.ed during hospita.iza.ion in survivors, ma.ing serum IL-17 concentra.ion a.potentia. bioma.ker for severity a.d response to trea.ment in IMHa.

关键词： a.toimmune disea.e ca.ine cytokines infla.ma.ion

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Compa.ion ca.ines: a. under-utilised model to a.d in tra.sla.ing a.ti-meta.ta.ics to the clinic

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CLINICa. & EXPERIMENTa. METa.Ta.IS 2020年第1期37卷 7-12页

作者： va. der Weyden, Louise Sta.key, Mike a.u-Helil, Bushra.Mutsa.rs, a.thony J. wood, geoffrey a. Wellcome Sanger Inst Expt Canc Genet T113 Wellcome Genome Campus Cambridge CB10 1SA England Anim Hlth Trust Lanwades Pk Newmarket CB8 7UU Suffolk England Univ Guelph Ontario Vet Coll Dept Clin Studies Guelph ON N1G 2W1 Canada Univ Guelph Ontario Vet Coll Pathobiol Dept Guelph ON N1G 2W1 Canada

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Loss of Erk3 function in mice lea.s to intra.terine growth restriction, pulmona.y imma.urity, a.d neona.a. letha.ity

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PROCEEDINGS OF THE Na.IONa. a.a.EMY OF SCIENCES OF THE UNITED STa.ES OF a.ERICA 2009年第39期106卷 16710-16715页

作者： Klinger, Sonia.Turgeon, Benja.in Levesque, Kim wood, geoffrey a. a.ga.rd-Tillery, Kjersti M. Meloche, Sylva.n Univ Montreal Inst Rech Immunol & Cancerol Montreal PQ H3C 3J7 Canada Univ Montreal Dept Pharmacol Montreal PQ H3C 3J7 Canada Univ Montreal Dept Mol Biol Montreal PQ H3C 3J7 Canada Univ Guelph Ontario Vet Coll Dept Pathobiol Guelph ON N1G 2W1 Canada Univ Utah Hlth Sci Dept Pediat Div Neonatol Salt Lake City UT 84112 USA Baylor Coll Med Dept Obstet & Gynecol Div Maternal Fetal Med Houston TX 77030 USA

Extra.ellula. signa.-regula.ed kina.e 3 (Erk3) is a. a.ypica. member of the mitogen-a.tiva.ed protein (Ma.) kina.e fa.ily. No function ha. yet been a.cribed to this Ma. kina.e. Here we show tha. ta.geted disruption of the Ma.k6 gene (encoding Erk3) lea.s to intra.terine growth restriction, a.socia.ed with ma.ked pulmona.y hypopla.ia. a.d ea.ly neona.a. dea.h during the first da. of life. a.ound 40% of Erk3(-/-) neona.es die within minutes a.ter birth from a.ute respira.ory fa.lure. Erk3-deficient mice ha.e norma. lung-bra.ching morphogenesis, but show dela.ed lung ma.ura.ion cha.a.terized by decrea.ed sa.cula.ion, a.electa.is, a.d defective type II pneumocyte differentia.ion. Interestingly, in utero a.ministra.ion of glucocorticoid promoted feta. lung ma.urity a.d rescued differentia.ion of type II cells, but fa.led to a.ter the neona.a. letha.ity. We observed tha. loss of Erk3 reta.ds intra.terine growth, a. reflected by a.ma.ked reduction in feta. lung, hea.t, a.d liver weights, a.d by low body weight a. birth. Importa.tly, we found tha. insulin-like growth fa.tor (IGF)-2 levels a.e decrea.ed in the serum of Erk3-deficient mice. Our findings revea. a.critica. role for Erk3 in the esta.lishment of feta. growth potentia. a.d pulmona.y function in the mouse.

关键词： gene ta.geting Ma. kina.e lung IUGR

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Reproducibility, sta.ility, a.d biologica. va.ia.ility of thrombin genera.ion using ca.ibra.ed a.toma.ed thrombogra.hy in hea.thy dogs

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VETERINa.Y CLINICa. Pa.HOLOGY 2018年第2期47卷 218-226页

作者： Cuq, Benoit Blois, Sha.na.L. wood, R. Da.ren Monteith, Ga.rielle a.ra.s-Ogg, a.thony C. Beda.d, Christia. wood, geoffrey a. Univ Guelph Dept Pathobiol Ontario Vet Coll Guelph ON Canada Univ Guelph Dept Clin Studies Ontario Vet Coll Guelph ON Canada Univ Montreal Fac Med Vet Dept Pathol & Microbiol Montreal PQ Canada

Ba.kgroundThrombin pla.s a.centra. role in hemosta.is a.d thrombosis. Ca.ibra.ed a.toma.ed thrombogra.hy (Ca.), a.thrombin genera.ion a.sa., ma. be a.useful test for hemosta.ic disorders in dogs. ObjectivesTo describe Ca. results in a.group of hea.thy dogs, a.d a.sess prea.a.ytica. va.ia.les a.d biologica. va.ia.ility. a.ima.sForty hea.thy dogs were enrolled. MethodsLa. time (La.), time to pea. (ttpea.), pea. thrombin genera.ion (pea.), a.d endogenous thrombin potentia. (ETP) were mea.ured. Direct jugula. venipuncture a.d winged-needle ca.heter-a.sisted sa.henous venipuncture were used to collect sa.ples from ea.h dog, a.d results were compa.ed between methods. Sa.ple sta.ility a. -80 degrees C wa. a.sessed over 12months in a.subset of sa.ples. Biologica. va.ia.ility of Ca. wa. a.sessed via.nested a.OVa.using sa.ples obta.ned weekly from a.subset of 9 dogs for 4 consecutive weeks. ResultsSa.ples for Ca. were sta.le a. -80 degrees C over 12months of stora.e. Sa.ples collected via.winged-needle ca.heter venipuncture showed poor repea.a.ility compa.ed to direct venipuncture sa.ples;there wa. a.so poor a.reement between the 2 sa.pling methods. Intra.individua. va.ia.ility of Ca. pa.a.eters wa. below 25%;inter-individua. va.ia.ility ra.ged from 36.9% to 78.5%. ConclusionsMea.urement of thrombin genera.ion using Ca. a.pea.s to be repea.a.le in hea.thy dogs, a.d sa.ples a.e sta.le for a. lea.t 12months when stored a. -80 degrees C. Direct venipuncture sa.pling is recommended for Ca.. Low indices of individua.ity suggest tha. subject-ba.ed reference interva.s a.e more suita.le when interpreting Ca. results.

关键词： Ca.ine hemosta.is

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