@article{gasior_hauck_bhattacharya_2022, title={Modeling the influence of cell-cell contact and TGF-beta signaling on the epithelial mesenchymal transition in MCF7 breast carcinoma cells}, volume={546}, ISSN={["1095-8541"]}, DOI={10.1016/j.jtbi.2022.111160}, abstractNote={The epithelial mesenchymal transition (EMT) is a process by which cells lose their adhesive nature and gain the migratory properties associated with mesenchymal cells. This transition allows cells to migrate away from a primary tumor while maintaining their newly acquired invasive behavior, suggesting that there is a bistable switch between the epithelial and mesenchymal phenotypes. In recent experimental work, we found evidence of this bistability in the MCF7 breast carcinoma cell line (Gasior et al., 2019). Underlying the complex processes governing EMT, we identify a feedback loop between E-cadherin, a protein involved in cellular adhesion, and Slug, a transcription factor that is upregulated during EMT. Here, we present a simple mathematical model that examines the relationship between E-cadherin and Slug in response to pro-epithelial and pro-mesenchymal factors, cell-cell contact and TGF-β, respectively. We hypothesize that cell-cell contact is a critical component in the transition from the epithelial to the mesenchymal phenotype and that it is possible to initiate EMT with the loss of cell-cell contact or the activation of the TGF-β signaling pathway. We propose a reversible bistable switch in response to a loss of cell-cell contact but an irreversible bistable switch when the cell is exposed to TGF-β. Taken together, this model shows that acquiring and retaining invasive behavior by cells with high levels of cell-cell contact is not impossible but, instead, depends on the cooperation between the two switches. The predictions of this model for E-cadherin and Slug levels were compared against relative gene expression data from our recent experiments with MCF7 cells (Gasior et al., 2019). Our model works well to predict E-cadherin and Slug mRNA expression in low confluence experiments, while also highlighting issues that arise when comparing experimental results to theoretical predictions.}, journal={JOURNAL OF THEORETICAL BIOLOGY}, author={Gasior, Kelsey and Hauck, Marlene and Bhattacharya, Sudin}, year={2022}, month={Aug} }
 @article{meuten_moore_donovan_bertram_klopfleisch_foster_smedley_dark_milovancev_stromberg_et al._2021, title={International Guidelines for Veterinary Tumor Pathology: A Call to Action}, ISSN={["1544-2217"]}, DOI={10.1177/03009858211013712}, abstractNote={Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website ( www.vetcancerprotocols.org ), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.}, journal={VETERINARY PATHOLOGY}, author={Meuten, Donald J. and Moore, Frances M. and Donovan, Taryn A. and Bertram, Christof A. and Klopfleisch, Robert and Foster, Robert A. and Smedley, Rebecca C. and Dark, Michael J. and Milovancev, Milan and Stromberg, Paul and et al.}, year={2021}, month={Jul} }
 @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.}, 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{gasior_wagner_cores_caspar_wilson_bhattacharya_hauck_2019, title={The role of cellular contact and TGF-beta signaling in the activation of the epithelial mesenchymal transition (EMT)}, volume={13}, ISSN={["1933-6926"]}, url={https://doi.org/10.1080/19336918.2018.1526597}, DOI={10.1080/19336918.2018.1526597}, abstractNote={ABSTRACT The epithelial mesenchymal transition (EMT) is one step in the process through which carcinoma cells metastasize by gaining the cellular mobility associated with mesenchymal cells. This work examines the dual influence of the TGF-β pathway and intercellular contact on the activation of EMT in colon (SW480) and breast (MCF7) carcinoma cells. While the SW480 population revealed an intermediate state between the epithelial and mesenchymal states, the MC7 cells exhibited highly adhesive behavior. However, for both cell lines, an exogenous TGF-β signal and a reduction in cellular confluence can push a subgroup of the population towards the mesenchymal phenotype. Together, these results highlight that, while EMT is induced by the synergy of multiple signals, this activation varies across cell types.}, number={1}, journal={CELL ADHESION & MIGRATION}, publisher={Informa UK Limited}, author={Gasior, Kelsey and Wagner, Nikki J. and Cores, Jhon and Caspar, Rose and Wilson, Alyson and Bhattacharya, Sudin and Hauck, Marlene L.}, year={2019}, pages={63–75} }
 @article{gasior_hauck_wilson_bhattacharya_2017, title={A Theoretical Model of the Wnt Signaling Pathway in the Epithelial Mesenchymal Transition}, volume={14}, ISSN={["1742-4682"]}, DOI={10.1186/s12976-017-0064-7}, abstractNote={Following the formation of a primary carcinoma, neoplastic cells metastasize by undergoing the epithelial mesenchymal transition (EMT), which is triggered by cues from inflammatory and stromal cells in the microenvironment. EMT allows epithelial cells to lose their highly adhesive nature and instead adopt the spindle-like appearance, as well as the invasive and migratory behavior, of mesenchymal cells. We hypothesize that a bistable switch between the epithelial and mesenchymal phenotypes governs EMT, allowing the cell to maintain its mesenchymal phenotype even after it leaves the primary tumor microenvironment and EMT-inducing extracellular signal.This work presents a simple mathematical model of EMT, specifically the roles played by four key proteins in the Wnt signaling pathway: Dishevelled (Dvl), E-cadherin, β-catenin, and Slug. The model predicts that following activation of the Wnt pathway, an epithelial cell in the primary carcinoma must attain a threshold level of membrane-bound Dvl to convert to the mesenchymal-like phenotype and maintain that phenotype once it has migrated away from the primary tumor. Furthermore, sensitivity analysis of the model suggests that in both the epithelial and the mesenchymal states, the steady state behavior of E-cadherin and the transcription factor Slug are sensitive to changes in the degradation rate of Slug, while E-cadherin is also sensitive to the IC50 (half-maximal) concentration of Slug necessary to inhibit E-cadherin production. The steady state behavior of Slug exhibits sensitivity to changes in the rate at which it is induced by β-catenin upon activation of the Wnt pathway. In the presence of sufficient amount of Wnt ligand, E-cadherin levels are sensitive to the ratio of the rate of Slug activation via β-catenin to the IC50 concentration of Slug necessary to inhibit E-cadherin production.The sensitivity of E-cadherin to the degradation rate of Slug, as well as the IC50 concentration of Slug necessary to inhibit E-cadherin production, shows how the adhesive nature of the cell depends on finely-tuned regulation of Slug. By highlighting the role of β-catenin in the activation of EMT and the relationship between E-cadherin and Slug, this model identifies critical parameters of therapeutic concern, such as the threshold level of Dvl necessary to inactivate the GSK-3β complex mediating β-catenin degradation, the rate at which β-catenin translocates to the nucleus, and the IC50 concentration of Slug needed to inhibit E-cadherin production.}, journal={THEORETICAL BIOLOGY AND MEDICAL MODELLING}, author={Gasior, Kelsey and Hauck, Marlene and Wilson, Alyson and Bhattacharya, Sudin}, year={2017}, month={Oct} }
 @article{kreilmeier_sampl_deloria_walter_reifinger_hauck_borst_holzmann_kleiter_2017, title={Alternative Lengthening of Telomeres Does Exist in Various Canine Sarcomas}, volume={56}, ISSN={["1098-2744"]}, url={http://europepmc.org/abstract/med/27585244}, DOI={10.1002/mc.22546}, abstractNote={Alternative lengthening of telomeres (ALT) is a telomere maintenance mechanism (TMM) found in some human tumors such as sarcomas. Canine tumors are not characterized for ALT and the study aim was to identify if the ALT phenotype exists in canine sarcomas. Sixty‐four canine sarcoma samples (20 snap‐frozen, 44 FFPE) as well as six canine sarcoma cell lines were screened for ALT by C‐circle assay. ALT was further evaluated by measuring telomere length via qPCR and telomere restriction‐fragments including pulsed‐field electrophoresis. ALT‐associated proteins were validated by immunohistochemistry. Further, telomerase activity (TA) and gene expression were analyzed by TRAP and qPCR. DNA from 20 human neuroblastomas and 8 sarcoma cell lines served as comparative controls. ALT was detected in 9.4% (6/64) canine sarcomas including aggressive subtypes as hemangiosarcoma, osteosarcoma, and histiocytic sarcoma. C‐circle levels were comparable with human ALT‐positive controls. All ALT tumors demonstrated loss of ATRX expression and 5/6 showed strong p53 expression. TA was detected in 93% (14/15) snap‐frozen samples including a sarcoma with ALT activity. This tumor showed long heterogeneous telomeres, and a high level of colocalization of DAXX with telomeres. One sarcoma was ALT and TA negative. All canine and human sarcoma cell lines were ALT negative. In this study, we demonstrated that canine sarcomas use ALT. As in humans, ALT was identified in aggressive sarcomas subtypes and coexisted with TA in one tumor. Overall, canine sarcomas seem to share many similarities with their human counterparts and appear an attractive model for comparative telomere research. © 2016 Wiley Periodicals, Inc.}, number={3}, journal={MOLECULAR CARCINOGENESIS}, author={Kreilmeier, Theresa and Sampl, Sandra and Deloria, Abigail J. and Walter, Ingrid and Reifinger, Martin and Hauck, Marlene and Borst, Luke B. and Holzmann, Klaus and Kleiter, Miriam}, year={2017}, month={Mar}, pages={923–935} }
 @article{hlavaty_wolfesberger_hauck_obermayer-pietsch_fuchs-baumgartinger_miller_walter_2017, title={Ezrin and moesin expression in canine and feline osteosarcoma}, volume={32}, number={8}, journal={Histology and Histopathology}, author={Hlavaty, J. and Wolfesberger, B. and Hauck, M. and Obermayer-Pietsch, B. and Fuchs-Baumgartinger, A. and Miller, I. and Walter, I.}, year={2017}, pages={805–816} }
 @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{boss_dewhirst_sampaio_bennett_tovmasyan_berman_beaven_rizzieri_batinic-haberle_hauck_et al._2017, title={Potential for a novel manganese porphyrin compound as adjuvant canine lymphoma therapy}, volume={80}, ISSN={["1432-0843"]}, DOI={10.1007/s00280-017-3372-z}, abstractNote={Manganese porphyrins are redox-active drugs and superoxide dismutase mimics, which have been shown to chemosensitize lymphoma, a cancer which frequently occurs in dogs. This study aimed to identify critical information regarding the pharmacokinetics and toxicity of Mn(III) meso-tetrakis (N-n-butoxyetylpyridium-2-yl) porphyrin, (MnTnBuOE-2-PyP5+, MnBuOE) in dogs as a prelude to a clinical trial in canine lymphoma patients. A single-dose pharmacokinetic (PK) study in normal dogs was performed to determine the plasma half-life (t 1/2) of MnBuOE. A dose reduction study was performed to establish the maximum tolerated dose (MTD) of MnBuOE. The safety and PK of a multi-dosing protocol was assessed. Peak plasma drug concentration occurred 30 min post-injection. The t 1/2 was defined as 7 h. MnBuOE induced an anaphylactic reaction and prolonged tachycardia. The MTD was defined as 0.25 mg/kg. The dogs were given MTD 3×/week for 2–3 weeks. The highest recorded tissue drug levels were in the lymph nodes (4–6 μM), followed by kidney and liver (2.5, 2.0 uM, respectively). We obtained critical information regarding the PK and toxicity of MnBuOE in dogs. The acute drug reaction and tachycardia post-injection have not been described in other species and may be specific to canines. The high tissue drug levels in lymph nodes have not been previously reported. MnBuOE accumulation in lymph nodes has important implications for the utility of adjuvant MnBuOE to treat lymphoma. With MnBuOE lymph node accumulation, reduction in the dose and/or administration frequency could be possible, leading to reduced toxicity.}, number={2}, journal={CANCER CHEMOTHERAPY AND PHARMACOLOGY}, author={Boss, M. K. and Dewhirst, M. W. and Sampaio, R. S. and Bennett, A. and Tovmasyan, A. and Berman, K. G. and Beaven, A. W. and Rizzieri, D. A. and Batinic-Haberle, I. and Hauck, M. L. and et al.}, year={2017}, month={Aug}, pages={421–431} }
 @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={Abstract}, 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{willcox_hammett-stabler_hauck_2016, title={Serum 25-hydroxyvitamin D concentrations in dogs with osteosarcoma do not differ from those of age- and weight-matched control dogs}, volume={217}, ISSN={["1532-2971"]}, DOI={10.1016/j.tvjl.2016.10.005}, abstractNote={Vitamin D concentrations show an inverse correlation with incidence of certain tumors in people and dogs. Additionally, human osteosarcoma has been associated with dysregulation of vitamin D-dependent pathways. The study objective was to compare serum 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in 20 dogs with osteosarcoma to age- and weight-matched control dogs. We hypothesized that dogs with osteosarcoma would have lower serum 25-hydroxyvitamin D than control dogs. The mean 25-hydroxyvitamin D3 concentrations for dogs with osteosarcoma and matched-controls were 34.95 ng/mL and 33.85 ng/mL, respectively (P = 0.784). Based on these data, 25-hydroxyvitamin D insufficiency might not be important in the pathogenesis of canine osteosarcoma.}, journal={VETERINARY JOURNAL}, author={Willcox, Jennifer L. and Hammett-Stabler, Catherine and Hauck, Marlene L.}, year={2016}, month={Nov}, pages={132–133} }
 @article{kreilmeier_mejri_hauck_kleiter_holzmann_2016, title={Telomere Transcripts Target Telomerase in Human Cancer Cells}, volume={7}, ISSN={["2073-4425"]}, DOI={10.3390/genes7080046}, abstractNote={Long non-coding transcripts from telomeres, called telomeric repeat-containing RNA (TERRA), were identified as blocking telomerase activity (TA), a telomere maintenance mechanism (TMM), in tumors. We expressed recombinant TERRA transcripts in tumor cell lines with TA and with alternative lengthening of telomeres (ALT) to study effects on TMM and cell growth. Adeno- and lentivirus constructs (AV and LV) were established for transient and stable expression of approximately 130 units of telomere hexanucleotide repeats under control of cytomegalovirus (CMV) and human RNase P RNA H1 (hH1) promoters with and without polyadenylation, respectively. Six human tumor cell lines either using telomerase or ALT were infected and analyzed for TA levels. Pre-infection cells using telomerase had 1%–3% of the TERRA expression levels of ALT cells. AV and LV expression of recombinant TERRA in telomerase positive cells showed a 1.3–2.6 fold increase in TERRA levels, and a decrease in TA of 25%–58%. Dominant-negative or small hairpin RNA (shRNA) viral expression against human telomerase reverse transcriptase (hTERT) results in senescence, not induced by TERRA expression. Population doubling time, cell viability and TL (telomere length) were not impacted by ectopic TERRA expression. Clonal growth was reduced by TERRA expression in TA but not ALT cell lines. ALT cells were not affected by treatments applied. Established cell models and tools may be used to better understand the role of TERRA in the cell, especially for targeting telomerase.}, number={8}, journal={GENES}, author={Kreilmeier, Theresa and Mejri, Doris and Hauck, Marlene and Kleiter, Miriam and Holzmann, Klaus}, year={2016}, month={Aug} }
 @article{schweiger_hauck_steinhoff_sampl_reifinger_walter_kreilmeier_marian_grusch_berger_et al._2015, title={Canine and human sarcomas exhibit predominant FGFR1 expression and impaired viability after inhibition of signaling}, volume={54}, ISSN={["1098-2744"]}, DOI={10.1002/mc.22155}, abstractNote={Fibroblast growth factor receptors (FGFRs) are important in malignant progression of several human epithelial tumors. However, little is known about FGFRs in canine or human soft tissue sarcomas. Thus, our aim was to investigate expression of FGFRs and their involvement in cell survival in sarcomas of both species. FGFR1–4 and FGFRL1 transcripts as well as IIIb/IIIc splice variants of FGFR1–3 were evaluated in 3 canine‐ and 6 human sarcoma cell lines and 19 spontaneous canine sarcomas by SYBRqPCR. FGFR1 protein expression was assessed by immunohistochemistry. Growth inhibitory effects of FGFR1 inhibitor PD166866 and dominant negative recombinant FGFR adenoviral expression constructs (dnFGFR) on tumor cell lines were analyzed. Profiling of multiple FGFR transcripts detected comparable co‐expression in most of human and canine sarcoma cell lines and canine tumor specimens. This indicates existence of closely related regulation mechanisms for FGFR expression in sarcomas of both species. FGFR1 with splice variant IIIc was consistently expressed with highest transcript levels. In 88% of the spontaneous tumor samples a heterogeneous FGFR1 protein expression was observed. Significant growth inhibition and cell death was seen after infection with dnFGFR1 in canine and human sarcoma cells, but not with dnFGFR3 and 4. PD166866 showed selective cytotoxicity with IC50 values between 12.1 and 26.4 μM. FGFR1 inhibition blocked ligand‐induced tyrosine phosphorylation of ERK1/2 mitogen‐activated protein kinase isoforms. This study emphasizes the important role FGFR1, especially splice variant IIIc, likely plays in sarcomas. Inhibitory small molecules could be of potential use for targeted therapy in aggressive sarcomas of both species. © 2014 Wiley Periodicals, Inc.}, number={9}, journal={MOLECULAR CARCINOGENESIS}, author={Schweiger, Nicole and Hauck, Marlene and Steinhoff, Heinrich and Sampl, Sandra and Reifinger, Martin and Walter, Ingrid and Kreilmeier, Theresa and Marian, Brigitte and Grusch, Michael and Berger, Walter and et al.}, year={2015}, month={Sep}, pages={841–852} }
 @article{milovancev_hauck_keller_stranahan_mansoor_malarkey_2015, title={Comparative Pathology of Canine Soft Tissue Sarcomas: Possible Models of Human Non-rhabdomyosarcoma Soft Tissue Sarcomas}, volume={152}, ISSN={["1532-3129"]}, DOI={10.1016/j.jcpa.2014.09.005}, abstractNote={Comparative analyses of canine and human soft tissue sarcomas (STSs) are lacking. This study compared the histological and immunohistochemical (labelling for desmin, smooth muscle actin [SMA], CD31, pancytokeratin, S100 and CD34) appearance of 32 archived, formalin-fixed, paraffin wax-embedded canine STS tumour specimens by board-certified veterinary and medical pathologists, both blinded to the other's interpretations. Comparison between the veterinary and human diagnoses revealed a generally consistent pattern of interpretation with few notable variations. Most tumours (13/32) were judged to display similar histomorphological appearance to human low-grade spindle cell sarcomas, appearing non-distinctive and morphologically of a fibroblastic/myofibroblastic type. Five canine cases resembled human liposarcoma, but with atypical desmin-positive epithelioid cells present. Five canine cases resembled human spindle cell sarcoma with myxoid features and two additional cases resembled human myxofibrosarcoma. Seven canine cases were noted to resemble human undifferentiated sarcoma. Findings in the present study demonstrate that canine STSs display histological and immunohistochemical features similar to their human equivalents. Because of these cross-species similarities, a particular opportunity exists to understand the biology and treatment of human STS by potentially including dogs as clinical models.}, number={1}, journal={JOURNAL OF COMPARATIVE PATHOLOGY}, author={Milovancev, M. and Hauck, M. and Keller, C. and Stranahan, L. W. and Mansoor, A. and Malarkey, D. E.}, year={2015}, month={Jan}, pages={22–27} }
 @article{thrall_maccarini_stauffer_macfall_hauck_snyder_case_linder_lan_mccall_et al._2012, title={Thermal dose fractionation affects tumour physiological response}, volume={28}, ISSN={["0265-6736"]}, DOI={10.3109/02656736.2012.689087}, abstractNote={Purpose: It is unknown whether a thermal dose should be administered using a few large fractions with higher temperatures or a larger number of fractions with lower temperatures. To evaluate this we assessed the effect of administering the same total thermal dose, approximately 30 CEM43T90, in one versus three to four fractions per week, over 5 weeks. Materials and methods: Canine sarcomas were randomised to receive one of the hyperthermia fractionation schemes along with fractionated radiotherapy. Tumour response was based on changes in tumour volume, oxygenation, water diffusion quantified using MRI, and a panel of histological and immunohistochemical end points. Results: There was a greater reduction in tumour volume and water diffusion at the end of therapy in tumours receiving one hyperthermia fraction per week. There was a weak but significant association between improved tumour oxygenation 24 h after the first hyperthermia treatment and extent of volume reduction at the end of therapy. Finally, the direction of change of HIF-1α and CA-IX immunoreactivity after the first hyperthermia fraction was similar and there was an inverse relationship between temperature and the direction of change of CA-IX. There were no significant changes in interstitial fluid pressure, VEGF, vWF, apoptosis or necrosis as a function of treatment group or temperature. Conclusions: We did not identify an advantage to a three to four per week hyperthermia prescription, and response data pointed to a one per week prescription being superior.}, number={5}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Thrall, Donald E. and Maccarini, Paolo and Stauffer, Paul and Macfall, James and Hauck, Marlene and Snyder, Stacey and Case, Beth and Linder, Keith and Lan, Lan and Mccall, Linda and et al.}, year={2012}, pages={431–440} }
 @article{chi_thrall_jiang_snyder_fels_landon_mccall_lan_hauck_macfall_et al._2011, title={Comparison of Genomics and Functional Imaging from Canine Sarcomas Treated with Thermoradiotherapy Predicts Therapeutic Response and Identifies Combination Therapeutics}, volume={17}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.ccr-10-2583}, abstractNote={Abstract}, number={8}, journal={CLINICAL CANCER RESEARCH}, author={Chi, Jen-Tsan and Thrall, Donald E. and Jiang, Chen and Snyder, Stacey and Fels, Diane and Landon, Chelsea and McCall, Linda and Lan, Lan and Hauck, Marlene and MacFall, James R. and et al.}, year={2011}, month={Apr}, pages={2549–2560} }
 @article{snyder_linder_hedan_hauck_2011, title={Establishment and Characterization of a Canine Soft Tissue Sarcoma Cell Line}, volume={48}, ISSN={["1544-2217"]}, DOI={10.1177/0300985810383871}, abstractNote={Stringently controlled in vitro experiments are a necessary part of translational research. Cell lines are useful for exploring the underlying biology of cancer. Very few canine soft tissue sarcoma cell lines exist. This report describes the establishment of a new canine soft tissue sarcoma cell line (MBSa1) derived from a high-grade, metastatic neurofibrosarcoma. The primary tumor tissue was obtained from a 12-year-old neutered male German Shepherd Dog and was maintained in tissue culture for a minimum of 20 passages over 7 months. MBSa1 was injected into athymic mice to determine tumorigenicity. Five million cells were injected into the subcutis of the right flank of athymic nude mice. Nine of the 10 mice grew tumors 1 cm or larger within 8 weeks of cell injection. The large number of in vitro passages coupled with solid tumor formation in athymic nude mice demonstrates that MBSa1 has been immortalized and is tumorigenic.}, number={2}, journal={VETERINARY PATHOLOGY}, author={Snyder, S. A. and Linder, K. and Hedan, B. and Hauck, M. L.}, year={2011}, month={Mar}, pages={482–485} }
 @article{dush_mciver_parr_young_fisher_newman_sannes_hauck_deiters_nascone-yoder_2011, title={Heterotaxin: A TGF-beta Signaling Inhibitor Identified in a Multi-Phenotype Profiling Screen in Xenopus Embryos}, volume={18}, ISSN={["1879-1301"]}, DOI={10.1016/j.chembiol.2010.12.008}, abstractNote={Disruptions of anatomical left-right asymmetry result in life-threatening heterotaxic birth defects in vital organs. We performed a small molecule screen for left-right asymmetry phenotypes in Xenopus embryos and discovered a pyridine analog, heterotaxin, which disrupts both cardiovascular and digestive organ laterality and inhibits TGF-β-dependent left-right asymmetric gene expression. Heterotaxin analogs also perturb vascular development, melanogenesis, cell migration, and adhesion, and indirectly inhibit the phosphorylation of an intracellular mediator of TGF-β signaling. This combined phenotypic profile identifies these compounds as a class of TGF-β signaling inhibitors. Notably, heterotaxin analogs also possess highly desirable antitumor properties, inhibiting epithelial-mesenchymal transition, angiogenesis, and tumor cell proliferation in mammalian systems. Our results suggest that assessing multiple organ, tissue, cellular, and molecular parameters in a whole organism context is a valuable strategy for identifying the mechanism of action of bioactive compounds.}, number={2}, journal={CHEMISTRY & BIOLOGY}, author={Dush, Michael K. and McIver, Andrew L. and Parr, Meredith A. and Young, Douglas D. and Fisher, Julie and Newman, Donna R. and Sannes, Philip L. and Hauck, Marlene L. and Deiters, Alexander and Nascone-Yoder, Nanette}, year={2011}, month={Feb}, pages={252–263} }
 @article{mahoney_fisher_snyder_hauck_2010, title={Feasibility of using gene expression analysis to study canine soft tissue sarcomas}, volume={21}, ISSN={["1432-1777"]}, DOI={10.1007/s00335-010-9298-y}, abstractNote={The prognosis given for canine soft tissue sarcomas (STSs) is based primarily on histopathologic grade. The decision to administer adjuvant chemotherapy is difficult since less than half of patients with high-grade STSs develop metastatic disease. We hypothesize that there is a gene signature that will improve our ability to predict development of metastatic disease in STS patients. The objective of this study was to determine the feasibility of using cDNA microarray and quantitative real-time PCR (qRT-PCR) analysis to determine gene expression patterns in metastatic versus nonmetastatic canine STSs, given the inherent heterogeneity of this group of tumors. Five STSs from dogs with metastatic disease were evaluated in comparison to eight STSs from dogs without metastasis. Tumor RNA was extracted, processed, and labeled for application to the Affymetrix Canine Genechip 2.0 Array. Array fluorescence was normalized using D-Chip software and data analysis was performed with JMP/Genomics. Differential gene expression was validated using qRT-PCR. Over 200 genes were differentially expressed at a false discovery rate of 5%. Differential gene expression was validated for five genes upregulated in metastatic tumors. Quantitative RT-PCR confirmed increased relative expression of all five genes of interest in the metastatic STSs. Our results demonstrate that microarray and qRT-PCR are feasible methods for comparing gene signatures in canine STSs. Further evaluation of the differences between gene expression in metastatic STSs and in nonmetastatic STSs is likely to identify genes that are important in the development of metastatic disease and improve our ability to prognosticate for individual patients.}, number={11-12}, journal={MAMMALIAN GENOME}, author={Mahoney, Jennifer A. and Fisher, Julie C. and Snyder, Stacey A. and Hauck, Marlene L.}, year={2010}, month={Dec}, pages={577–582} }
 @article{snyder_dewhirst_hauck_2008, title={The role of hypoxia in canine cancer}, volume={6}, ISSN={["1476-5829"]}, DOI={10.1111/j.1476-5829.2008.00163.x}, abstractNote={Abstract}, number={4}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, author={Snyder, S. A. and Dewhirst, M. W. and Hauck, M. L.}, year={2008}, month={Dec}, pages={213–223} }
 @article{siddiqui_li_larue_poulson_avery_pruitt_zhang_ullrich_thrall_dewhirst_et al._2007, title={A phase I trial of hyperthermia-induced interleukin-12 gene therapy in spontaneously arising feline soft tissue sarcomas}, volume={6}, ISSN={["1535-7163"]}, DOI={10.1158/1535-7163.MCT-06-0342}, abstractNote={Abstract}, number={1}, journal={MOLECULAR CANCER THERAPEUTICS}, author={Siddiqui, Farzan and Li, Chuan-Yuan and LaRue, Susan M. and Poulson, Jean M. and Avery, Paul R. and Pruitt, Amy F. and Zhang, Xiuwu and Ullrich, Robert L. and Thrall, Donald E. and Dewhirst, Mark W. and et al.}, year={2007}, month={Jan}, pages={380–389} }
 @article{phillips_stephenson_hauck_dillberger_2007, title={Heritability and segregation analysis of osteosarcorna in the Scottish deerhound}, volume={90}, ISSN={["0888-7543"]}, DOI={10.1016/j.ygeno.2007.05.001}, abstractNote={Osteosarcoma is the most common malignant bone tumor in dogs and, like its human orthologue, is characterized by aggressive local behavior and high metastatic rates. The Scottish deerhound is a breed of dog with a >15% incidence of osteosarcoma and represents an excellent spontaneously occurring large-animal model of the human disease. We modeled the transmission of the osteosarcoma phenotype in a population of over 1000 related deerhounds ascertained as part of a prospective health study. Variance component analysis, segregation analysis, and linear modeling were performed to evaluate heritability, to infer the presumptive transmission model, and to identify covariate effects for this phenotype within the breed, respectively. Based on variance component analysis, heritability (h2) was estimated to be 0.69. Six transmission models were analyzed by segregation analysis; based on Akaike's information criteria, the most parsimonious model was the Mendelian major gene model with dominant expression. Linear modeling identified gender and genotype as significant predictors of disease outcome. Importantly, duration of gonadal hormone exposure, weight, and height at maturity were not significant predictors of outcome. Inheritance of the putative high-risk allele was thus associated with >75% risk of disease occurrence compared to the <5% baseline risk. These results support the hypothesis that a major gene with a dominant effect explains most of the osteosarcoma phenotype within the Scottish deerhound.}, number={3}, journal={GENOMICS}, author={Phillips, Jeffrey C. and Stephenson, Betty and Hauck, Marlene and Dillberger, John}, year={2007}, month={Sep}, pages={354–363} }
 @article{kleiter_yu_mohammadian_niehaus_spasojevic_sanders_viglianti_yarmolenko_hauck_petry_et al._2006, title={A tracer dose of technetium-99m-labeled liposomes can estimate the effect of hyperthermia on intratumoral Doxil extravasation}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-06-0839}, abstractNote={Abstract}, number={22}, journal={CLINICAL CANCER RESEARCH}, author={Kleiter, Miriam M. and Yu, Daohai and Mohammadian, Lenore A. and Niehaus, Nelsen and Spasojevic, Ivan and Sanders, Linda and Viglianti, Benjamin L. and Yarmolenko, Pavel S. and Hauck, Marlene and Petry, Neil A. and et al.}, year={2006}, month={Nov}, pages={6800–6807} }
 @article{hauck_larue_petros_poulson_yu_spasojevic_pruitt_klein_case_thrall_et al._2006, title={Phase I trial of doxorubicin-containing low temperature sensitive liposomes in spontaneous canine tumors}, volume={12}, ISSN={["1078-0432"]}, DOI={10.1158/1078-0432.CCR-06-0226}, abstractNote={Abstract}, number={13}, journal={CLINICAL CANCER RESEARCH}, author={Hauck, Marlene L. and LaRue, Susan M. and Petros, William P. and Poulson, Jean M. and Yu, Daohai and Spasojevic, Ivan and Pruitt, Amy F. and Klein, Allison and Case, Beth and Thrall, Donald E. and et al.}, year={2006}, month={Jul}, pages={4004–4010} }
 @article{heller_stebbins_reynolds_hauck_2005, title={A retrospective study of 87 cases of canine soft tissue sarcomas, 1986-2001}, volume={3}, ISBN={1542-2666}, number={2}, journal={International Journal of Applied Research in Veterinary Medicine}, author={Heller, D. A. and Stebbins, M. E. and Reynolds, T. L. and Hauck, M. L.}, year={2005}, pages={81–87} }
 @article{hauck_zalutsky_2005, title={Enhanced tumour uptake of radiolabelled antibodies by hyperthermia. Part II: Application of the thermal equivalency equation}, volume={21}, ISSN={["1464-5157"]}, DOI={10.1080/02656730400011032}, abstractNote={Clinical application of local hyperthermia as a means for modulating drug and macro-molecular tumour uptake have been slow to develop, due in part to the difficulty in designing and comparing heating protocols. The thermal isodose formula developed by Sapareto and Dewey is used in cytotoxicity and radiosensitization hyperthermia protocols to compare different time/temperature combinations; however, its relevance to other end-points has not been evaluated. The current study was undertaken to determine whether heating protocols of different time and temperature, but predicted to be thermally equivalent by this formula, had similar effects on the tumour and normal tissue distribution of radiolabelled tumour-specific (anti-tenascin 81C6) and non-specific (anti-dansyl TPS3.2) monoclonal antibodies (mAbs). Two thermally equivalent heating protocols, 4 h at 41.8°C and 45 min at 43°C, were compared in mice with subcutaneous D54 MG human glioma xenografts. A 4-fold increase in xenograft localization of 81C6 mAb was achieved relative to that in non-heated control groups with both heating protocols. Both hyperthermia protocols also resulted in improved tumour:normal tissue ratios. However, differences in absolute tumour and normal tissue uptake were seen, suggesting that the thermal isodose formula has limited usefulness in the design and comparison of hyperthermia protocols for enhancing the tumour uptake of radiolabelled mAbs.}, number={1}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Zalutsky, MR}, year={2005}, month={Feb}, pages={13–27} }
 @article{hauck_zalutsky_2005, title={Enhanced tumour uptake of radiolabelled antibodies by hyperthermia: Part I: Timing of injection relative to hyperthermia}, volume={21}, ISSN={["1464-5157"]}, DOI={10.1080/02656730410001695906}, abstractNote={Improving drug and macromolecular delivery of anti-cancer agents to tumours results in greater efficacy without increased toxicity. The current study was undertaken to assess the effects of the timing of injection of tumour specific and non-specific monoclonal antibodies (mAbs) relative to a hyperthermia treatment on tumour and normal tissue uptake. Using a local hyperthermia protocol of 45 min at 43°C, uptake in tumour and normal tissues was measured at 1, 4, 12, 24, 48 and 72 h after injection. An anti-tenascin chimeric mAb, ch81C6, served as the specific mAb in a D-54 MG glioma xenograft mouse model. The chimeric mAb chTPS3.2 served as the control. A five-to-eight-fold increase in uptake of the tumour-targeted mAb was achieved in the heated tumours when compared with the non-heated tumours at 1 h. Differences in absolute tumour uptake of the specific mAb between the mice injected prior to hyperthermia and mice injected post-hyperthermia were seen only at 1 and 12 h. The median uptakes in the tumours of mice injected pre-heat were 25%ID/g at 1 h and 43.5%ID/g at 12 h, while in the animals injected post-hyperthermia the median uptakes were 45.5%ID/g and 80.2%ID/g, respectively. Blood levels of both the specific and non-specific mAbs were consistently higher over the initial 12 h period in the mice injected post-hyperthermia. Normal tissue uptake was also increased at most time points in the mice injected post-hyperthermia. The clinical importance of the differences in specific mAb uptake in tumour detected statistically at 1 and 12 h is questionable, given the highly variable nature of mAb uptake in vivo. Tumour targeting mAbs administered in combination with heat may be injected either prior to or immediately following hyperthermia treatment, with the expectation that levels of uptake in tumour will be relatively equivalent. Absolute normal tissue levels will be higher in patients receiving the mAb post-hyperthermia.}, number={1}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Zalutsky, MR}, year={2005}, month={Feb}, pages={1–11} }
 @article{thrall_larue_yu_samulski_sanders_case_rosner_azuma_poulson_pruitt_et al._2005, title={Thermal dose is related to duration of local control in canine sarcomas treated with thermoradiotherapy}, volume={11}, number={14}, journal={Clinical Cancer Research}, author={Thrall, D. E. and Larue, S. M. and Yu, D. H. and Samulski, T. and Sanders, L. and Case, B. and Rosner, G. and Azuma, C. and Poulson, J. and Pruitt, A. F. and et al.}, year={2005}, pages={5206–5214} }
 @article{williams_johnson_hauck_ruslander_price_thrall_2004, title={Chemotherapy followed by half-body radiation therapy for canine lymphoma}, volume={18}, ISSN={["1939-1676"]}, DOI={10.1892/0891-6640(2004)18<703:CFBHRT>2.0.CO;2}, abstractNote={A protocol of induction chemotherapy followed by half-body radiation therapy for treatment of lymphoma was used in 94 dogs. Seventy-three (78%) dogs achieved complete remission. Substage (P = .011) and phenotype (P = .015) were identified as predictors of complete remission rate. Of these, 52 dogs received half-body irradiation. Cranial and caudal halves received a total dose of 8.0 Gy, given in 2 fractions of 4.0 Gy on consecutive days with cobalt-60 photons and a 3-week interval between halves. Median 1st remission for these dogs was 311 days. Anemia was identified as the only predictor for length of 1st remission (P = .024). Toxicoses after half-body irradiation generally were mild and infrequent and included myelosuppression and gastrointestinal signs. Thirty-one dogs relapsed and 20 resumed treatment with induction followed by maintenance chemotherapy. Seventeen (85%) dogs achieved a 2nd complete remission. Median overall remission for all 52 dogs was 486 days. Results of this study suggest that half-body radiation therapy after induction chemotherapy is well tolerated and might increase remission duration compared with conventional protocols that use chemotherapy alone, but this increase might not be long enough to be clinically relevant or to justify application of the method described herein.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Williams, LE and Johnson, JL and Hauck, ML and Ruslander, DM and Price, GS and Thrall, DE}, year={2004}, pages={703–709} }
 @article{proulx_ruslander_dodge_hauck_williams_horn_price_thrall_2003, title={A retrospective analysis of 140 dogs with oral melanoma treated with external beam radiation}, volume={44}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2003.tb00468.x}, abstractNote={Despite the early notion that canine oral malignant melanoma is radioresistant, recent data suggest that external beam radiotherapy is effective in local tumor control. However, optimal fractionation schedules have not been established. The high rate of regional and distant metastasis is another problem that has hindered long‐term control. The role of chemotherapy in the management of canine oral melanoma has also not been determined. In this study, data from 140 dogs irradiated at North Carolina State University were evaluated with the following objectives: (1) to compare the efficacy of three radiation therapy protocols (36 Gy, 9 Gy × 4 fractions; 30 Gy, 10 Gy × 3 fractions; or >45 Gy, 2–4 Gy × 12–19 fractions) for the treatment of dogs with oral malignant melanoma, (2) to identify any host or tumor factors influencing prognosis, and (3) to determine the impact of systemic chemotherapy on treatment outcome. Information regarding response to therapy, disease progression, and survival were determined from the medical records or from information obtained by telephone or mail survey. Relationships between host, tumor, and treatment variables and outcome measures (response, time to first event, and survival) were evaluated using Fisher's exact test (response) and the Cox regression model (time to first event and survival). The median time to first event for the 140 dogs was 5.0 months (95% C.I., 4–6 months) and the median survival was 7.0 months (95% C.I., 6–9 months). In the univariate analysis, the following variables were associated with increased time to first event and survival: (1) rostral tumor sublocation; (2) lack of bone lysis observed on skull imaging, and (3) microscopic tumor burden. In a multivariate analysis of 111 dogs with complete data for these variables, tumor sublocation, bone lysis, and tumor volume were identified as joint predictors of time to first event (p<.001,p<.001, andp= .04, respectively) and survival (p<.001,p<.001, andp= 05, respectively). There were no differences in response, time to first event and survival between the three radiation therapy protocols used. Systemic chemotherapy had no impact on the development of metastatic disease, time to first event, or survival, although the dosages used in this study were suboptimal. External beam radiation therapy is effective in local disease control of canine oral malignant melanoma; however, the optimal fractionation scheme has yet to be determined. The high metastatic rate observed with this disease and the inefficacy of systemic chemotherapy indicate that further investigation into novel therapies is warranted.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Proulx, DR and Ruslander, DM and Dodge, RK and Hauck, ML and Williams, LE and Horn, B and Price, GS and Thrall, DE}, year={2003}, pages={352–359} }
 @article{bailey_erb_williams_ruslander_hauck_2003, title={Carboplatin and doxorubicin combination chemotherapy for the treatment of appendicular osteosarcoma in the dog}, volume={17}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2003)017<0199:CADCCF>2.3.CO;2}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Bailey, D and Erb, H and Williams, L and Ruslander, D and Hauck, M}, year={2003}, pages={199–205} }
 @article{hauck_2003, title={Feline injection site sarcomas}, volume={33}, ISSN={["1878-1306"]}, DOI={10.1016/S0195-5616(03)00006-8}, abstractNote={Injection site sarcomas in cats have been the topic of more than 40 articles and over 20 scientific abstracts as well as multiple letters to veterinary journals, articles in the popular press, and Internet-based web sites. With the level of discussion that has surrounded this tumor entity, one might expect that great strides have been made in determining the etiology, epidemiology, and preferred treatment options for this disease. Nearly half of the publications on this subject are review articles, however, and that alone indicates both the high level of interest and the lack of information in this situation. This article summarizes the development of our current understanding of this tumor with regard to areas of research into the cause of injection site sarcomas, epidemiology, and the current standard of care for treatment of this iatrogenic disease.}, number={3}, journal={VETERINARY CLINICS OF NORTH AMERICA-SMALL ANIMAL PRACTICE}, author={Hauck, M}, year={2003}, month={May}, pages={553-+} }
 @inbook{hauck_2003, title={Injection site sarcomas}, booktitle={Veterinary clinics of North america--update in Medical Oncology}, author={Hauck, M. L.}, year={2003}, pages={553–571} }
 @article{kobayashi_hauck_dodge_page_price_williams_hardie_mathews_thrall_2002, title={Preoperative radiotherapy for vaccine associated sarcoma in 92 cats}, volume={43}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.2002.tb01036.x}, abstractNote={Medical records for 92 cats with a vaccine associated sarcoma receiving preoperative irradiation, with or without chemotherapy, between December 1985 and September 1998 were reviewed. The purposes were to quantify response to treatment and to attempt identify‐cation of factors associated with favorable response. Variables evaluated for a relationship to outcome included signalment, tumor location, presence of gross vs. microscopic tumor, radiation field size, irradiation technique, type of surgical procedure, completeness of excision, and chemotherapy (none, carboplatin alone, and others). Time to first event was calculated for the first day of treatment until local tumor recurrence or metastasis, or the date of euthanasia or death. Median time to first event for all 92 cats was 584 days. Only completeness of surgical excision was related to the time to first event. Median time to first event in cats having complete surgical excision was 986 days compared to 292 days for cats with incomplete excision (P = 0.004). Cats requiring bone removal to effect tumor removal had earlier failure than cats having other types of surgery. There was not a significant relationship between administration of chemotherapy or chemotherapy type and time to first event although outcome in cats receiving carboplatin was better than all other treatment groups. Carboplatin addition to preoperative irradiation appears worthy of further study. Pre‐operative irradiation is an effective treat‐ment for cats with vaccine associated sarcoma, especially if complete excision can be accomplished following irradiation.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Kobayashi, T and Hauck, ML and Dodge, R and Page, RL and Price, GS and Williams, LE and Hardie, EM and Mathews, KG and Thrall, DE}, year={2002}, pages={473–479} }
 @article{defrancesco_atkins_keene_coats_hauck_2002, title={Prospective clinical evaluation of serum cardiac troponin T in dogs admitted to a veterinary teaching hospital}, volume={16}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2002)016<0553:PCEOSC>2.3.CO;2}, abstractNote={The purpose of this study was to measure serum cardiac troponin T (cTnT) with a commercially available human enzyme-linked immunoassay (ELISA) test in various groups of dogs, including those undergoing doxorubicin chemotherapy. Serum samples were obtained from 6 groups of dogs: (1) normal adult dogs (n = 15); (2) dogs with asymptomatic dilated cardiomyopathy (n = 5); (3) dogs with congestive heart failure (n = 10); (4) dogs with untreated neoplasia (n = 20); (5) dogs with skeletal muscle trauma (n = 10); and (6) dogs with neoplasia receiving doxorubicin chemotherapy (n = 4). One serum sample was obtained from each of the normal dogs, those with asymptomatic cardiomyopathy, those with congestive heart failure, and those with untreated neoplasia. Serum samples were obtained serially from the dogs that were undergoing doxorubicin chemotherapy; samples were collected before doxorubicin (30 mg/m2) administration and then 1, 5, 7, and 14 days after administration throughout 6 cycles for a cumulative total dose of 180 mg/m2. All normal dogs, dogs with untreated neoplasia, and dogs with asymptomatic dilated cardiomyopathy had cTnT concentrations below the lower limits of detection for the assay used (<0.05 ng/mL). Detectable concentrations of cTnT were found in 3 dogs with congestive heart failure and in 2 dogs with skeletal muscle trauma. Detectable concentrations also were found in both dogs that had received 180 mg/m2 of doxorubicin. We conclude that dogs with congestive heart failure and those with skeletal muscle trauma and dogs with neoplasia receiving high-dose doxorubicin chemotherapy may have increased serum cTnT concentration, which may be suggestive of myocardial damage.}, number={5}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={DeFrancesco, TC and Atkins, CE and Keene, BW and Coats, JR and Hauck, ML}, year={2002}, pages={553–557} }
 @article{dickerson_page_ladue_hauck_thrall_stebbins_price_2001, title={Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs}, volume={15}, ISSN={["0891-6640"]}, DOI={10.1892/0891-6640(2001)015<0120:RAOASO>2.3.CO;2}, abstractNote={Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.}, number={2}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Dickerson, ME and Page, RL and LaDue, TA and Hauck, ML and Thrall, DE and Stebbins, ME and Price, GS}, year={2001}, pages={120–124} }
 @article{case_hauck_yeager_simkins_serres_schmith_dillberger_page_2000, title={The pharmacokinetics and pharmacodynamics of GW395058, a peptide agonist of the thrombopoietin receptor, in the dog, a large-animal model of chemotherapy-induced thrombocytopenia}, volume={18}, ISSN={["1066-5099"]}, DOI={10.1634/stemcells.18-5-360}, abstractNote={GW395058, a PEGylated peptide agonist of the thrombopoietin receptor, stimulates megakaryocytopoiesis and has previously been shown to increase platelet counts in vivo. The pharmacokinetics and pharmacodynamics of GW395058 were characterized using a randomized, crossover study in a large‐animal model (dog) of chemotherapy‐induced thrombocytopenia.}, number={5}, journal={STEM CELLS}, author={Case, BC and Hauck, ML and Yeager, RL and Simkins, AH and Serres, M and Schmith, VD and Dillberger, JE and Page, RL}, year={2000}, pages={360–365} }
 @article{ladue_dodge_page_price_hauck_thrall_1999, title={Factors influencing survival after radiotherapy of nasal tumors in 130 dogs}, volume={40}, ISSN={["1058-8183"]}, DOI={10.1111/j.1740-8261.1999.tb00367.x}, abstractNote={Improvements in survival of dogs with nasal tumors have been slow to develop throughout the past three decades. Despite multiple studies examining various radiation time‐dose schema, the advancement of CT‐based computerized treatment planning, and the evaluation of detailed staging systems, the optimal treatment regimen, and most important prognostic factors regarding survival remain unclear. In this study, data from four previous studies were combined with data from 44 additional dogs, and this population of 130 dogs was evaluated for factors which influenced survival. Twenty‐one dogs were treated with orthovoltage at the University of Pennsylvania. One hundred nine dogs were treated with cobalt photons at North Carolina State University. Sixty‐five of these 109 dogs had been previously described. Of the 44 dogs not previously described, 35 were treated with a shrinking field technique. Survival was determined from the medical record, or from information derived by telephone or mail survey. The univariate Cox regression model was used to examine for relationship between various patient, tumor, and treatment variables and survival. Significant relationships identified in the univariate analysis were further analyzed using the multivariate Cox regression model. Median survival of the 130 dogs was 8.9 months (95% C.I., 8–11 months). In the univariate analysis, the following variables were associated with decreased survival: 1) age >10 years old, 2) regional lymph node metastasis, 3) advanced tumor stage, 4) use of megavoltage radiation, 5) overall total dose >55 Gray, and 6) boost technique performed. In a multivariate analysis of 125 dogs with complete data for age, radiation type, and radiation dose, age (p< .001) and radiation type (p = .02) were identified as joint predictors of survival. After adjusting for age, the staging system lost prognostic significance (p = .06). In a subset of dogs that received cobalt radiation, after adjusting for age, dogs treated with a boost technique had decreased survival (p = .001). In general, local control of canine nasal tumors following aggressive radiation therapy is poor. Early diagnosis and selection of appropriate patients is warranted and palliative types of treatment should be considered in dogs with a poor chance of long term survival.}, number={3}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={LaDue, TA and Dodge, R and Page, RL and Price, GS and Hauck, ML and Thrall, DE}, year={1999}, pages={312–317} }
 @article{ramirez_dodge_page_price_hauck_ladue_nutter_thrall_1999, title={Palliative radiotherapy of appendicular osteosarcoma in 95 dogs}, volume={40}, ISSN={["1740-8261"]}, DOI={10.1111/j.1740-8261.1999.tb00385.x}, abstractNote={Ninety‐five dogs with either a presumptive (n= 24) or biopsy confirmed diagnosis (n= 71) of soteosarcoma received palliative radiotherapy using60Co photons. Parallel opposed beams were used with each dog receivign either 10 Gy on days 0,7 and 21 (n= 58) or 8 Gy on days 0 and 7 (n= 37). The 8 Gy fractionation scheme was given with the intent of retreating upon relapse from pain relief. Only 9 of 37 (24%) dogs in the 8 Gy group returned for retreatment, Forty‐seven of the 95 dogs (49%) received concurrent or sequention chemotherapy. Seventy of the 95 dogs (74%) experienced pain relief following treatment. In dogs experiencing pain relief the median duration of response was 73 days. Numerous clinical variables were evaluated as predictors of response. The only variable significantly related to achieving a response was the use of chemotheraphy. The following variables were significanly related to the duration of response: extent of bone lysis, chemotherapy use, length of bone involved and tumor site (humerus). In a multivariate analysis (n= 73 dogs), after adjusting for chemotherapy use, extent of bone involvement (p= 0.01) and tumor site (p= 0.02) retained statistical significance, while degree of bone lysis did not (p= 0.11). No difference in response incidence or duration was found between 3 fractions of 10 Gy vs. 2 fractions of 8 Gy. Administration of a low initial dose with the intent of retreatment was not a successful strategy.}, number={5}, journal={VETERINARY RADIOLOGY & ULTRASOUND}, author={Ramirez, O and Dodge, RK and Page, RL and Price, GS and Hauck, ML and LaDue, TA and Nutter, F and Thrall, DE}, year={1999}, pages={517–522} }
 @article{hauck_larsen_welsh_zalutsky_1998, title={Cytotoxicity of alpha-particle emitting astatine-211-labelled antibody in tumour spheroids: no effect of hyperthermia}, volume={77}, ISSN={["0007-0920"]}, DOI={10.1038/bjc.1998.123}, abstractNote={The high linear energy transfer, alpha-particle-emitting radionuclide astatine-211 (211At) is of interest for certain therapeutic applications; however, because of the 55- to 70-microm path length of its alpha-particles, achieving homogeneous tracer distribution is critical. Hyperthermia may enhance the therapeutic efficacy of alpha-particle endoradiotherapy if it can improve tracer distribution. In this study, we have investigated whether hyperthermia increased the cytotoxicity of an 211At-labelled monoclonal antibody (MAb) in tumour spheroids with a radius (approximately 100 microm) greater than the range of 211At alpha-particles. Hyperthermia for 1 h at 42 degrees C was used because this treatment itself resulted in no regrowth delay. Radiolabelled chimeric MAb 81C6 reactive with the extracellular matrix antigen tenascin was added to spheroids grown from the D-247 MG human glioma cell line at activity concentrations ranging from 0.125 to 250 kBq ml(-1). A significant regrowth delay was observed at 125 and 250 kBq ml(-1) in both hyperthermia-treated and untreated spheroids. For groups receiving hyperthermia, no increase in cytotoxicity was seen compared with normothermic controls at any activity concentration. These results and those from autoradiographs indicate that hyperthermia at 42 degrees C for 1 h had no significant effect on the uptake or distribution of this antitenascin MAb in D-247 MG spheroids.}, number={5}, journal={BRITISH JOURNAL OF CANCER}, author={Hauck, ML and Larsen, RH and Welsh, PC and Zalutsky, MR}, year={1998}, month={Mar}, pages={753–759} }
 @article{hauck_zalutsky_1998, title={The effects of local hyperthermia on the catabolism of a radioiodinated chimeric monoclonal antibody}, volume={4}, journal={Clinical Cancer Research}, author={Hauck, M. L. and Zalutsky, M. R.}, year={1998}, pages={2071–2077} }
 @article{hauck_coffin_dodge_dewhirst_mitchell_zalutsky_1997, title={A local hyperthermia treatment which enhances antibody uptake in a glioma xenograft model does not affect tumour interstitial fluid pressure}, volume={13}, ISSN={["0265-6736"]}, DOI={10.3109/02656739709023538}, abstractNote={Solid tumours have an elevated interstitial fluid pressure (IFP) due to the lack of normal lymphatics, increased permeability of tumour vasculature and an expanding cell population within a potentially limited space. This elevated IFP has been proposed to be an important barrier to the delivery of drugs and marcromolecules. We have demonstrated that local hyperthermia (4 h, 41.8 degrees C) is capable of significantly enhancing the uptake of radiolabelled monoclonal antibodies (mAbs) in D-54 MG glioma xenografts grown subcutaneously in athymic mice. To determine if this increased uptake was attributable to alterations in the tumour IFP, pressure measurements using the wick-in-needle technique were made in tumours after hyperthermia treatment. These pressure measurements were taken at various time points from 4 to 90 h following the initiation of the hyperthermia and compared with pressures taken concurrently in untreated tumours. In addition, pressures were measured following a 2 h, 41.8 degrees C hyperthermia treatment, a protocol which does not result in elevated uptake of radiolabeled mAbs. No significant differences were seen at any time point in IFP measured in the tumours receiving either hyperthermia treatment when compared with untreated tumours. Thus, we conclude that the mechanism by which this hyperthermia regimen enhances mAb uptake in this human glioma xenograft model is not due to alternations in tumour IFP.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Coffin, DO and Dodge, RK and Dewhirst, MW and Mitchell, JB and Zalutsky, MR}, year={1997}, pages={307–316} }
 @article{hauck_dewhirst_bigner_zaultsky_1997, title={Local hyperthermia improves uptake of a chimeric monoclonal antibody in a subcutaneous xenograft model}, volume={3}, journal={Clinical Cancer Research}, author={Hauck, M. L. and Dewhirst, M. W. and Bigner, D. D. and Zaultsky, M. R.}, year={1997}, pages={63–70} }
 @article{hauck_price_ogilvie_johnson_gillette_thrall_dewhirst_page_1996, title={Phase I evaluation of mitoxantrone alone and combined with whole body hyperthermia in dogs with lymphoma}, volume={12}, ISSN={["0265-6736"]}, DOI={10.3109/02656739609022520}, abstractNote={The maximum tolerated dose of mitoxantrone (MX) administered alone or combined with whole body hyperthermia (WBH) was determined in this nonrandomized, prospective study in dogs with lymphoma. MX was administered to 53 dogs every three weeks for a total of six treatments unless progressive disease or persistent, severe toxicity developed. Fifty dogs were evaluable (MX alone n = 30, MX/WBH n = 20). MX was administered as a 1 h infusion at the onset of the plateau phase of WBH in dogs treated with combined therapy. Dogs were evaluated weekly between treatments for the first four treatments with physical examination and complete blood counts to define acute and cumulative toxicity. Dogs were evaluated every three weeks for tumour response until relapse. The maximum tolerated dose (MTD) was defined as that dose in each group that resulted in a 50% incidence of moderate or severe toxicity as estimated from logistic regression analysis of the toxicity data. Myelosuppression was the only toxicity observed. Neutropenia was equal in frequency and severity between treatment groups. Thrombocytopenia was not observed in any dog receiving MX/WBH but occurred in 13% of dogs treated with MX alone. The MTD for MX +/- WBH was 6.1 +/- 0.6 and 6.5 +/- 0.8mg/M2 respectively. A steeper dose response relationship was observed in dogs receiving combined therapy compared to dogs treated with MX alone suggesting WBH may improve the uniformity of patient response to chemotherapy. We concluded that MX may be administered without dose reduction to dogs undergoing WBH and that MX should be evaluated more thoroughly in future thermochemotherapy studies.}, number={3}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={Hauck, ML and Price, GS and Ogilvie, GK and Johnson, J and Gillette, EL and Thrall, DE and Dewhirst, MW and Page, RL}, year={1996}, pages={309–320} }
 @article{hauck_dewhirst_zalutsky_1996, title={The effects of clinically relevant hyperthermic temperatures on the kinetic binding parameters of a monoclonal antibody}, volume={23}, ISSN={["0883-2897"]}, DOI={10.1016/0969-8051(96)00039-x}, abstractNote={Hyperthermia is a therapeutic modality under investigation for its ability to increase absolute levels of tumor uptake of radiolabeled monoclonal antibodies (MAbs). We have investigated whether hyperthermia may affect the binding parameters of MAbs. The effects of clinically relevant levels of hyperthermia on the kinetic binding parameters were investigated for 81C6, an antibody undergoing Phase I/II clinical trials for the treatment of brain tumors and neoplastic meningitis. No obvious effects of temperature in either the association or dissociation rate constants, nor in the equilibrium constants, were apparent between 37 ° and 45 °C. The improved binding stability of the bivalent form of the MAb was apparent when compared with its monovalent Fab fragment.}, number={4}, journal={NUCLEAR MEDICINE AND BIOLOGY}, author={Hauck, ML and Dewhirst, MW and Zalutsky, MR}, year={1996}, month={May}, pages={551–557} }
 @inbook{hauck_dewhirst_zalutsky_1995, title={Enhancement of radiolabeled monoclonal antibody uptake in tumors with local hyperthermia}, booktitle={Handbook of targeted delivery of imaging agents}, author={Hauck, M. L. and Dewhirst, M. W. and Zalutsky, M. R.}, year={1995}, pages={333–359} }
 @article{page_mcentee_williams_george_price_novotney_hauck_riviere_dewhirst_thrall_1994, title={EFFECT OF WHOLE-BODY HYPERTHERMIA ON CARBOPLATIN DISPOSITION AND TOXICITY IN DOGS}, volume={10}, ISSN={["0265-6736"]}, DOI={10.3109/02656739409012373}, abstractNote={Fifty dogs with refractory or disseminated spontaneous tumours were evaluated in two independent phase I studies using either carboplatin (CBDCA) alone or CBDCA plus whole body hyperthermia (WBH). CBDCA was administered as a 30 min infusion at the onset of the plateau phase of WBH in dogs receiving combined treatment. Serum samples were collected and drug disposition was determined in both treatment groups. The dose-effect relationship was mathematically described with a logistic regression model developed from categorical toxicity data accumulated throughout the first two treatment courses in all dogs. The maximum tolerated dose (MTD) was defined as that dose which resulted in a 50% probability of achieving moderate or severe toxicity. The only toxicities observed were neutropenia and thrombocytopenia, which were dose-dependent. The nadir occurred between 7 and 14 days following treatment. A significant decrease in the area under the serum CBDCA versus time curve for dogs undergoing WBH was consistent with increased tissue binding of the drug as well as increased urinary eliminations. Serum AUC values determined following the first course of treatment were predictive of subsequent toxicity in both treatment groups. The MTD (95%CI) for CBDCA and CBDCA/WBH were estimated to be 318(44) and 239(51) mg/M2 respectively (p = 0.08). A randomized phase II evaluation should be initiated to determine if a therapeutic gain can be achieved using combined CBDCA and WBH. Further refinement of the CBDCA dose in such a trial should be based on both pharmacokinetic parameters and normal tissue response.}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and MCENTEE, MC and WILLIAMS, PL and GEORGE, SL and PRICE, GS and NOVOTNEY, CA and HAUCK, ML and RIVIERE, JE and DEWHIRST, MW and THRALL, DE}, year={1994}, pages={807–816} }
 @article{page_thrall_george_price_heidner_mcentee_novotney_hauck_dewhirst_1992, title={QUANTITATIVE ESTIMATION OF THE THERMAL DOSE-MODIFYING FACTOR FOR CIS-DIAMMINEDICHLOROPLATINUM (CDDP) IN TUMOR-BEARING DOGS}, volume={8}, ISSN={["0265-6736"]}, DOI={10.3109/02656739209005024}, abstractNote={A statistical method for estimating clinical toxicity was used to determine a theoretical isoeffect dose-modifying factor for dogs with disseminated or refractory neoplasia treated with cis-diammine dichloroplatinum (II) plus whole-body hyperthermia or CDDP alone. CDDP was administered every 3 weeks with vigorous saline hydration to 54 dogs (CDDP alone n = 21, CDDP/WBH n = 33) that were eligible for entry into this non-randomized study. CDDP was administered during the plateau phase of WBH in dogs receiving combined therapy. Acute toxicity included myelosuppression (CDDP n = 7; CDDP/WBH n = 5), nephrotoxicity (CDDP n = 1, CDDP/WBH n = 1) and respiratory distress (CDDP/WBH n = 2). Eight dogs experienced chronic renal dysfunction as a result of CDDP (n = 2) or CDDP/WBH (n = 6). A theoretical thermal dose-modifying factor was determined for both acute and cumulative toxicity by comparing the maximum tolerated dose of each treatment group. The maximum tolerated dose (MTD) of CDDP +/- WBH was defined as that dose producing a 50% incidence of moderate acute toxicity or acute plus mild chronic toxicity as estimated from logistic regression analysis of the toxicity data. The MTD (+/- .standard error) of CDDP/WBH for acute toxicity only was 54.6 (4.3) mg/M2 and for CDDP alone the MTD was 73.6 (40) mg/M2. Thus, the isoeffect dose-modifying factor for acute toxicity was 1.35 (0.12). The MTD (SE) of CDDP/WBH for cumulative toxicity (acute plus chronic toxicity) was 46.4 (2.7) mg/M2 and for CDDP alone waas 70.0 (2.9) mg/M2. The isoeffect dose-modifying factor for total cumulative toxicity was 1.5 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)}, number={6}, journal={INTERNATIONAL JOURNAL OF HYPERTHERMIA}, author={PAGE, RL and THRALL, DE and GEORGE, SL and PRICE, GS and HEIDNER, GL and MCENTEE, MC and NOVOTNEY, CA and HAUCK, ML and DEWHIRST, MW}, year={1992}, pages={761–769} }