@inproceedings{lai_kent_nolan_fu_looper_2024, title={Long-term survival of adrenal tumors treated with stereotactic body radiation therapy}, booktitle={Veterinary Cancer Society Annual Conference}, author={Lai, Yen-Hao and Kent, Michael and Nolan, Michael and Fu, Dah-Renn and Looper, Jayme}, year={2024} }
 @article{meneses_gidcumb_marcus_gonzalez_lai_mishra_lascelles_nolan_2023, title={Acute radiotherapy-associated oral pain may promote tumor growth at distant sites}, volume={13}, ISSN={["2234-943X"]}, url={http://dx.doi.org/10.3389/fonc.2023.1029108}, DOI={10.3389/fonc.2023.1029108}, abstractNote={IntroductionPatients developing acute radiotherapy induced dermatitis or oral mucositis commonly experience pain. When severe, this radiotherapy-associated pain (RAP) can necessitate treatment breaks; unfortunately, in a variety of cancers, prolongation of the radiotherapy course has been associated with early cancer relapse and/or death. This is often attributed to accelerated repopulation, but it is unknown whether pain or pain signaling constituents might alter tumor behavior and hasten metastatic disease progression. We studied this by testing the hypothesis that severe acute RAP at one site can hasten tumor growth at a distant site.MethodsMice underwent single fraction tongue irradiation (27 Gy, or 0 Gy “sham” control) to induce severe glossitis. At the time of maximal oral RAP, one of three luciferase-transfected tumor cell lines were injected via tail vein (4T1, B16F10, MOC2; each paired to their syngeneic host: BALB/c or C57BL/6); tumor burden was assessed via in vivo transthoracic bioluminescence imaging and ex vivo pulmonary nodule quantification. Survival was compared using Kaplan-Meier statistics.ResultsTongue irradiation and resultant RAP promoted lung tumor growth of 4T1-Luc2 cells in BALB/c mice. This effect was not a result of off-target radiation, nor an artefact of environmental stress caused by standard (subthermoneutral) housing temperatures. RAP did not affect the growth of B16F10-Luc2 cells, however, C57BL/6 mice undergoing tail vein injection of MOC2-Luc2 cells at the time of maximal RAP experienced early lung tumor-attributable death. Lung tumor growth was normalized when RAP was reduced by treatment with resiniferatoxin (300 µg/kg, subcutaneously, once).DiscussionThis research points towards radiation-induced activation of capsaicin-responsive (TRPV1) neurons as the cause for accelerated growth of tumors at distant (unirradiated) sites.}, journal={FRONTIERS IN ONCOLOGY}, publisher={Frontiers Media SA}, author={Meneses, Constanza S. and Gidcumb, Emily M. and Marcus, Karen L. and Gonzalez, Yarines and Lai, Yen Hao and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2023}, month={May} }
 @inproceedings{lai_lyles_mitchell_looper_2023, title={Effects of half body irradiation on remission and survival for dogs with high grade lymphoma}, booktitle={American College of Veterinary Radiology Annual Scientific Meeting}, author={Lai, Yen-Hao and Lyles, Sarah and Mitchell, Mark and Looper, Jayme}, year={2023} }
 @inproceedings{lai_looper_2023, title={The management of canine thymoma with intensity-modulated radiation therapy (IMRT)}, booktitle={House Officer Seminar, Louisiana State University}, author={Lai, Yen-Hao and Looper, Jayme}, year={2023} }
 @inproceedings{lai_looper_2022, title={Canine adrenal gland tumors treated with radiation therapy}, booktitle={House Officer Seminar. Louisiana State University}, author={Lai, Yen-Hao and Looper, Jayme}, year={2022} }
 @inproceedings{lai_looper_2022, title={Strontium-90, a unique radiation modality treating cancers in dogs and cats}, booktitle={House Officer Seminar. Louisiana State University,}, author={Lai, Yen-Hao and Looper, Jayme}, year={2022} }
 @article{lai_lascelles_nolan_2021, title={Behavioral phenotyping of cancer pain in domesticated cats with naturally occurring squamous cell carcinoma of the tongue: initial validation studies provide evidence for regional and widespread algoplasticity}, volume={9}, ISSN={["2167-8359"]}, url={http://dx.doi.org/10.7717/peerj.11984}, DOI={10.7717/peerj.11984}, abstractNote={Feline oral squamous cell carcinoma (FOSCC) is a common and naturally occurring condition that recapitulates many features of human head and neck cancer (HNC). In both species, there is need for improved strategies to reduce pain caused by HNC and its treatment. Research to benefit both species could be conducted using pet cats as a comparative model, but this prospect is limited by lack of validated methods for quantifying FOSCC-associated pain. A prospective non-randomized pilot study was performed for initial validation of: (1) a pet owner administered quality of life questionnaire and visual assessment scoring tool (FORQ/CLIENT); (2) a clinician assessment questionnaire (UFEPS/VET); (3) electronic von Frey testing [EVF]; and (4) Cochet-Bonnet (COBO) aesthesiometry. To assess intra-rater reliability, discriminatory ability, and responsiveness of each assay, 6 cats with sublingual SCC and 16 healthy control cats were enrolled. The intra-rater reliability was moderate-to-good for the clinical metrology instruments and EVF (intraclass correlation coefficient [ICC] ≥ 0.68), but poor for COBO (ICC = 0.21). FORQ/CLIENT scores were higher (worse quality of life) in FOSCC cats vs healthy controls. The internal reliability of FORQ/CLIENT scoring was high (Cronbach α = 0.92); sensitivity and specificity were excellent (100% when using cut-offs determined using receiver operating characteristic [ROC] curves). For the FORQ/CLIENT, there was strong and inverse correlation between scores from the questions and visual assessment (r =  − 0.77, r2 = 0.6, P < 0.0001). For the UFEPS/VET, Cronbach’s α was 0.74 (high reliability). Sensitivity and specificity were 100% and 94%, respectively, when using a cut-off score (3.5) based on ROC curves (Youden index of 0.94). Total UFEPS/VET scores were positively correlated with FORQ/CLIENT scores (r2 = 0.72, P < 0.0001). Sensitivity of EVF and COBO ranged from 83 to 100% and specificity ranged from 56 to 94%. Cats with cancer were more sensitive around the face (lower response thresholds) and on the cornea (longer filament lengths) than control animals (P < 0.03). Reduced pressure response thresholds were also observed at a distant site (P = 0.0002) in cancer cats. After giving buprenorphine, EVF pressure response thresholds increased (P = 0.04) near the mandible of cats with OSCC; the length of filament required to elicit a response in the COBO assay also improved (shortened; P = 0.017). Based on these preliminary assessments, the assays described herein had reasonable inter-rater reliability, and they were able to both discriminate between cats with and without oral cancer, and respond in a predictable manner to analgesic therapy. In cats with tongue cancer, there was evidence for regional peripheral sensitization, and widespread somatosensory sensitization. These results provide a basis for multi-dimensional assessments of pain and sensitivity in cats with oral SCC.}, journal={PEERJ}, publisher={PeerJ}, author={Lai, Yen-Hao Erik and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Aug} }
 @inproceedings{lai_looper_2021, title={Half body irradiation in lymphoma patients}, booktitle={House Officer Seminar. Louisiana State University}, author={Lai, Yen-Hao and Looper, Jayme}, year={2021} }
 @article{lai_baumer_meneses_roback_robertson_mishra_lascelles_nolan_2021, title={Irradiation of the Normal Murine Tongue Causes Upregulation and Activation of Transient Receptor Potential (TRP) Ion Channels}, volume={196}, ISSN={["1938-5404"]}, url={http://dx.doi.org/10.1667/rade-21-000103.1}, DOI={10.1667/rade-21-000103.1}, abstractNote={Signal transduction at sensory neurons occurs via transmembrane flux of cations, which is largely governed by the transient receptor potential (TRP) family of ion channels. It is unknown whether TRP channel activation contributes to the pain that accompanies radiation-induced oral mucositis. This study sought to characterize changes in TRP channel expression and function that occur in the locally irradiated tissues and afferent neurons of mice. Female CD-1 mice received single high-dose (27 Gy) tongue irradiation, or sham irradiation. Animals were euthanized either before overt glossitis developed (days 1 and 5 postirradiation), when glossitis was severe (day 11), or after mice had recovered (days 21 and 45). Tongue irradiation caused upregulation of the Trpv1 gene in trigeminal ganglia (TG) neurons. Other TRP genes (Trpv2, Trpv4, Trpa1, Trpm8) and Gfrα3 (which acts upstream of several TRP channels) were also upregulated in TGs and/or tongue tissue, in response to radiation. Ex vivo calcium imaging experiments demonstrated that the proportions of TG neurons responding to histamine (an activator of TRPV1, TRPV4 and TRPA1), TNF-α (an activator of TRPV1, TRPV2 and TRPV4), and capsaicin (a TRPV1 agonist), were increased as early as one day after tongue irradiation; these changes persisted for at least 21 days. In a subsequent experiment, we found that genetic deletion of TRPV1 mitigated weight loss (a surrogate marker of pain severity) in mice with severe glossitis. The results intimate that various TRP channels, and TRPV1 in particular, should be explored as analgesic targets for patients experiencing pain after oral irradiation.}, number={4}, journal={RADIATION RESEARCH}, publisher={Radiation Research Society}, author={Lai, Yen and Baumer, Wolfgang and Meneses, Constanza and Roback, Donald M. and Robertson, James B. and Mishra, Santosh K. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2021}, month={Oct}, pages={331–344} }
 @article{lai_morhard_ramanujam_nolan_2021, title={Minimally invasive ethyl cellulose ethanol ablation in domesticated cats with naturally occurring head and neck cancers: Six cats}, volume={19}, ISSN={["1476-5829"]}, url={http://dx.doi.org/10.1111/vco.12687}, DOI={10.1111/vco.12687}, abstractNote={AbstractIt is difficult to retain tumoricidal doses of ethanol in large or unencapsulated tumours without causing intoxication or damaging surrounding tissue. Ethyl cellulose‐ethanol ablation (ECEA) overcomes this limitation by trapping ethanol intratumorally. To evaluate the safety of ECEA and to develop a clinically feasible workflow, a single‐arm pilot study was performed in cats with lingual/sublingual squamous cell carcinoma (SCC). Six cats underwent intratumoral injection of 6% ethyl cellulose in ethanol. Subjects were observed overnight. There was mild bleeding and transient hyperthermia, and injection site pain and swelling that improved with anti‐inflammatory drugs. Serum ethanol was minimally elevated; the mean concentration peaked 1 hour after injection (129 +/− 15.1 nM). Cats were rechecked at weeks 1 and 2; booster treatments were given in cats (n = 3) with stable quality of life and partial response to therapy. Recheck examinations were then performed monthly. The longest tumour dimension increased in each animal (progressive disease via cRECIST); however, estimated tumour volume was reduced in 3 of 6 cats, within 1 week of ECEA. All cats were euthanized (median survival time 70 days) because of local tumour progression and/or lingual dysfunction that was likely hastened by ECEA. ECEA is not a viable treatment for feline lingual/sublingual SCC; tumour volume was effectively reduced in some cats, but the simultaneous loss of lingual function was poorly tolerated. Further optimization may make ECEA a useful option for SCC at other oral sites in the cat, and for head and neck malignancies in other species.}, number={3}, journal={VETERINARY AND COMPARATIVE ONCOLOGY}, publisher={Wiley}, author={Lai, Yen-Hao Erik and Morhard, Robert and Ramanujam, Nirmala and Nolan, Michael W.}, year={2021}, month={Sep}, pages={492–500} }
 @article{price_lai_marcus_robertson_lascelles_nolan_2020, title={Early radiation‐induced oral pain signaling responses are reduced with pentoxifylline treatment}, volume={62}, ISSN={1058-8183 1740-8261}, url={http://dx.doi.org/10.1111/vru.12943}, DOI={10.1111/vru.12943}, abstractNote={AbstractRadiation‐induced acute oral mucositis is associated with inflammation and pain. In other realms of pain research, nociceptors are known to be activated by inflammatory cytokines; for example, tumor necrosis factor alpha (TNF‐α) can activate transient receptor potential ion channels on sensory neurons. But there is an unclear relationship between inflammatory cytokines and molecular mediators of pain in radiation‐induced mucositis (RIM) and radiation‐associated pain (RAP). In this prospective, analytical, experimental pilot study, a common drug (pentoxifylline [PTX]) was used with the goal of inhibiting TNF‐α signaling in mice that underwent lingual irradiation to induce severe acute oral RIM/RAP. Body weight and glossitis scores were recorded daily. Eye wiping behaviors were assayed as a surrogate measure of oral discomfort (which is possible due to cross‐sensitization of the mandibular and ophthalmic branches of the trigeminal nerve). Quantitative real‐time reverse transcription polymerase chain reaction was performed on irradiated tongue tissue to measure changes in expression of TNF‐α, its receptor, nuclear factor kappa‐light‐chain‐enhancer of activated B cells, transient receptor potential vanilloid type 1 (TRPV1), and transient receptor potential vanilloid type 4 (TRPV4). Responsiveness of afferent sensory trigeminal neurons to TNF‐α, a TRPV1 agonist (capsaicin), and a partial TRPV4 agonist (histamine) was measured via calcium imaging. Although PTX treatment did not reduce glossitis severity or mitigate weight loss in mice with RIM/RAP, it did inhibit the upregulation of TNF‐α’s receptor that normally accompanies RIM, and it also reduced neuronal responsiveness to each of the aforementioned chemical stimuli. These results provide provisional evidence that inhibition of TNF‐α signaling with PTX treatment may serve as a useful tool for reducing pain in head and neck cancer patients.}, number={2}, journal={Veterinary Radiology & Ultrasound}, publisher={Wiley}, author={Price, Mikayla L. and Lai, Yen‐Hao (Erik) and Marcus, Karen L. and Robertson, James B. and Lascelles, B. Duncan X. and Nolan, Michael W.}, year={2020}, month={Dec}, pages={255–263} }
 @inproceedings{lai_duncan_lascelles_nolan_2019, title={Cellular and molecular mechanisms of pain caused by acute radiation injuries}, booktitle={American College of Veterinary Radiology Annual Scientific Meeting}, author={Lai, Yen-Hao and Duncan, B. and Lascelles, X. and Nolan, Michael W.}, year={2019} }
 @phdthesis{lai_2019, title={Mechanisms and Models of Pain in Head and Neck Cancer Irradiation}, school={Comparative Biomedical Sciences, North Carolina State University}, author={Lai, Y.H.}, year={2019} }
 @inproceedings{lai_duncan_lascelles_nolan_2019, title={Orofacial pain assessment in cats with tongue cancers}, booktitle={College of Veterinary Medicine Research Forum}, author={Lai, Yen-Hao and Duncan, B. and Lascelles, X. and Nolan, Michael W.}, year={2019} }
 @article{lai_morhard_ramanujam_duncan_lascelles_nolan_2019, title={Preclinical optimization of an enhanced ethanol ablation technique in a large animal spontaneous disease model of human head and neck cancer}, journal={Consortium for Canine Comparative Oncology}, author={Lai, Erik Yen-Hao and Morhard, Robert and Ramanujam, Nimmi and Duncan, B. and Lascelles, X. and Nolan, Michael W.}, year={2019} }
 @inproceedings{lai_duncan_lascelles_nolan_2019, title={Quantify orofacial pain in feline head and neck cancer}, booktitle={Pain in Animal Workshop}, author={Lai, Yen-Hao and Duncan, B. and Lascelles, X. and Nolan, Michael W.}, year={2019} }
 @inproceedings{lai_washburn_marcus_nolan_2018, title={Irradiation triggers trpv1 and trpv4 activation that is related to discomfort and pain}, booktitle={Consortium for Canine Comparative Oncology}, author={Lai, Yen-Hao and Washburn, Jenna and Marcus, Karen and Nolan, Michael W.}, year={2018} }
 @inproceedings{lai_nolan_2018, title={Radiotherapy-induced mucositis and pain are associated with TRPV1 and TRPV4 activation}, booktitle={Radiation Research Society Annual International Meeting}, author={Lai, Erik Yen-Hao and Nolan, Michael W.}, year={2018} }
 @inproceedings{lai_nolan_2018, title={Upregulation of TRPV1 and TRPV4 in Radiation-induced Mucositis and Pain}, booktitle={American Society for Radiation Oncology, Tumor Microenvironment Workshop}, author={Lai, Erik Yen-Hao and Nolan, Michael W.}, year={2018} }
 @inproceedings{lai_nolan_2017, title={Improvement on a murine model for studying radiation-induced oral mucositis and associated discomfort}, booktitle={Radiation Research Society Annual International Meeting}, author={Lai, Yen-Hao and Nolan, Michael}, year={2017} }
 @inproceedings{lai_nolan_2017, title={Low-dose total body irradiation alters the sensitivity of sensory trigeminal ganglia neurons to chemical stimuli}, booktitle={College of Veterinary Medicine Research Forum}, author={Lai, Yen-Hao and Nolan, Michael W.}, year={2017} }
 @inproceedings{lai_chen_hsu_chang_2015, title={Detection of MAGE-A in Normal Canine Tissues by Real-time Polymerase Chain Reaction}, booktitle={Spring Conference of Chinese Society of Veterinary Medicine}, author={Lai, Yen-Hao and Chen, Yi-Chen and Hsu, Wei-Li and Chang, Shih-Chieh}, year={2015} }
 @phdthesis{lai_hsu_chang_2015, title={Detection of MAGE-A in Normal Canine Tissues by Reverse Transcription-Polymerase Chain Reaction}, school={National Chung-Hsing University}, author={Lai, Y.H. and Hsu, W.L. and Chang, S.C.}, year={2015} }
 @inproceedings{lai_chang_2014, title={Detection of MAGE-A in Normal Mammalian Tissues}, booktitle={Seminar of Veterinary Medicine Master Program, College of Veterinary Medicine}, author={Lai, Yen-Hao and Chang, Shih-Chieh}, year={2014} }
 @inproceedings{lai_lee_2013, title={Thoracolumbar Spinal Intervertebral Disk Disease in Two Dachshunds}, booktitle={Clinical Conference, College of Veterinary Medicine}, author={Lai, Yen-Hao and Lee, Wei-Ming}, year={2013} }
 @inproceedings{lai_chan_2012, title={Conjunctival Squamous Cell Carcinoma and Phlebothrombosis in a Hanoverian Horse}, booktitle={Clinical Conference, College of Veterinary Medicine}, author={Lai, Yen-Hao and Chan, Jacky Peng-Wen}, year={2012} }