Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma.
Abstract: Integrated time nanosecond pulse irreversible electroporation (INSPIRE) is a novel tumor ablation modality that employs high voltage, alternating polarity waveforms to induce cell death in a well-defined volume while sparing the underlying tissue. This study aimed to demonstrate the in vivo efficacy of INSPIRE against spontaneous melanoma in standing, awake horses. Unassigned: A custom applicator and a pulse generation system were utilized in a pilot study to treat horses presenting with spontaneous melanoma. INSPIRE treatments were administered to 32 tumors across 6 horses and an additional 13 tumors were followed to act as untreated controls. Tumors were tracked over a 43-85 day period following a single INSPIRE treatment. Pulse widths of 500ns and 2000ns with voltages between 1000 V and 2000 V were investigated to determine the effect of these variables on treatment outcomes. Unassigned: Treatments administered at the lowest voltage (1000 V) reduced tumor volumes by 11 to 15%. Higher voltage (2000 V) treatments reduced tumor volumes by 84 to 88% and eliminated 33% and 80% of tumors when 500 ns and 2000 ns pulses were administered, respectively. Unassigned: Promising results were achieved without the use of chemotherapeutics, the use of general anesthesia, or the need for surgical resection in regions which are challenging to keep sterile. This novel therapeutic approach has the potential to expand the role of pulsed electric fields in veterinary patients, especially when general anesthesia is contraindicated, and warrants future studies to demonstrate the efficacy of INSPIRE as a solid tumor treatment.
Copyright © 2024 Fesmire, Peal, Ruff, Moyer, McParland, Derks, O’Neil, Emke, Johnson, Ghosh, Petrella, DeWitt, Prange, Fogle and Sano.
Publication Date: 2024-01-30 PubMed ID: 38352036PubMed Central: PMC10861690DOI: 10.3389/fvets.2024.1232650Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research article discusses a novel technique called Integrated Time Nanosecond Pulse Irreversible Electroporation (INSPIRE) for effectively treating spontaneous melanoma in horses. The technique uses high voltage, alternating polarity waveforms which causes controlled cell death, while leaving the surrounding tissue unharmed.
Methodology and Test Subjects
- The researchers used a unique applicator and a pulse generation system in a pilot study which involved horses diagnosed with spontaneous melanoma.
- A total of 32 tumors across 6 horses were treated using the INSPIRE technique, while an additional 13 tumors were left untreated to serve as control.
- The condition of the tumors was monitored over a period of 43 to 85 days after a single INSPIRE treatment.
Treatment Parameters and Effects
- The researchers played around with pulse widths of 500ns and 2000ns and voltages between 1000 V and 2000 V to study their influence on the results of the treatment.
- It was observed that treatments given at the lowest voltage of 1000 V reduced the size of the tumors by 11 to 15%.
- Treatments given at a higher voltage of 2000 V, however, proved to be more effective, causing tumor volumes to reduce by 84 to 88%.
- Specially, on administering 2000 V with 500 ns and 2000 ns pulses, 33% and 80% of the tumors respectively were completely eliminated.
Significance and Future Prospects of INSPIRE
- INSPIRE has proved to be a promising method of tumor treatment without involving the use of chemotherapeutics, general anesthesia, or surgical resections in areas that are difficult to maintain sterile.
- This technique can potentially broaden the role of pulsed electric fields in veterinary treatment especially in scenarios where general anesthesia can’t be used.
- The success of INSPIRE as observed in the pilot study calls for further research into its efficacy as a solid tumor treatment method.
Cite This Article
APA
Fesmire CC, Peal B, Ruff J, Moyer E, McParland TJ, Derks K, O'Neil E, Emke C, Johnson B, Ghosh S, Petrella RA, DeWitt MR, Prange T, Fogle C, Sano MB.
(2024).
Investigation of integrated time nanosecond pulse irreversible electroporation against spontaneous equine melanoma.
Front Vet Sci, 11, 1232650.
https://doi.org/10.3389/fvets.2024.1232650 Publication
Researcher Affiliations
- Bioelectricity Lab, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Clinical Studies Core, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Clinical Studies Core, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Bioelectricity Lab, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States.
- Bioelectricity Lab, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States.
- Bioelectricity Lab, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Department of Clinical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
- Bioelectricity Lab, UNC/NCSU Joint Department of Biomedical Engineering, Raleigh, NC, United States.
- Department of Molecular Biomedical Sciences, NC State College of Veterinary Medicine, Raleigh, NC, United States.
Grant Funding
- R01 CA272550 / NCI NIH HHS
- R01 CA276232 / NCI NIH HHS
Conflict of Interest Statement
CFe, RP, MD, and MS have intellectual property related to this manuscript and may receive royalties. MD and MS have ownership in Gradient Medical Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
References
This article includes 98 references
- Sullins KE. Melanocytic tumours in horses. Equine Vet Educ (2019) 32:624–30.
- van der Weyden L, Patton EE, Wood GA, Foote AK, Brenn T, Arends MJ. Cross-species models of human melanoma. J Pathol (2016) 238:152–65.
- MacKay RJ. Treatment options for melanoma of gray horses. Vet Clin Equine Pract (2019) 35:311–25.
- Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer MH. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse. Nat Genet (2008) 40:1004–9.
- Curik I, Druml T, Seltenhammer M, Sundström E, Pielberg GR, Andersson L. Complex inheritance of melanoma and pigmentation of coat and skin in grey horses. PLoS Genet (2013) 9:e1003248.
- Rowe EL, Sullins KE. Excision as treatment of dermal melanomatosis in horses: 11 cases (1994–2000). J Am Vet Med Assoc (2004) 225:94–6.
- Johnson PJ. Dermatologic tumors (excluding sarcoids). Vet Clin N Am Equine Pract (1998) 14:625–58.
- Scott DW. Large animal dermatology. (1988).
- Sundberg J, Burnstein T, Page E, Kirkham W, Robinson F. Neoplasms of equidae. J Am Vet Med Assoc (1977) 170:150–2.
- Pimenta J, Prada J, Cotovio M. Equine melanocytic tumors: a narrative review. Animals (2023) 13:247.
- Smith S, Goldschmidt M, McManus P. A comparative review of melanocytic neoplasms. Vet Pathol (2002) 39:651–78.
- Gorham S, Robl M. Melanoma in the gray horse: the darker side of equine aging. Vet Med (1986).
- Valentine BA. Equine melanocytic tumors: a retrospective study of 53 horses (1988 to 1991). J Vet Intern Med (1995) 9:291–7.
- Hewes CA. Review of the treatment of equine cutaneous neoplasia. AAEP Proceedings (2009).
- Groom L, Sullins K. Surgical excision of large melanocytic tumours in grey horses: 38 cases (2001–2013). Equi Vet Educ (2018) 30:438–43.
- Théon AP, Wilson WD, Magdesian KG, Pusterla N, Snyder JR, Galuppo LD. Long-term outcome associated with intratumoral chemotherapy with cisplatin for cutaneous tumors in equidae: 573 cases (1995–2004). J Am Vet Med Assoc (2007) 230:1506–13.
- Hewes CA, Sullins KE. Use of cisplatin-containing biodegradable beads for treatment of cutaneous neoplasia in equidae: 59 cases (2000–2004). J Am Vet Med Assoc (2006) 229:1617–22.
- Melanomas JK. Current therapy in equine medicine. Philadelphia: WB Saunders Co; (1997).
- Milner R, Salute M, Crawford C, Abbot J, Farese J. The immune response to disialoganglioside GD3 vaccination in normal dogs: a melanoma surface antigen vaccine. Vet Immunol Immunopathol (2006) 114:273–84.
- Trinchieri G. Proinflammatory and immunoregulatory functions of interleukin-12. Int Rev Immunol (1998) 16:365–96.
- Rubio-Martinez LM, Hendrickson DA. Complications in equine surgery. Hoboken, NJ: John Wiley & Sons; (2021).
- Cryosurgery RB. Cryosurgery. Annu Rev Biomed Eng (2000) 2:157–87.
- Steponkus PL. Role of the plasma membrane in freezing injury and cold acclimation. Annu Rev Plant Physiol (1984) 35:543–84.
- Hoffmann NE, Bischof JC. The cryobiology of cryosurgical injury. Urology (2002) 60:40–9.
- Rabb J, Renaud M, Brandt P, Witt C. Effect of freezing and thawing on the microcirculation and capillary endothelium of the hamster cheek pouch. Cryobiology (1974) 11:508–18.
- Nagle WA, Soloff BL, Moss A, Jr, Henle KJ. Cultured Chinese hamster cells undergo apoptosis after exposure to cold but nonfreezing temperatures. Cryobiology (1990) 27:439–51.
- Roberts KP, Smith DJ, Ozturk H, Kazem A, Pazhayannur PV, Hulbert JC. Biochemical alterations and tissue viability in AT-1 prostate tumor tissue after in vitro cryodestruction. Cryo-Letters (1997) 18:241–50.
- Theon A. Cisplatin treatment for cutaneous tumors. Curr Ther Equine Med (1997) 4:372–7.
- Coughlin CM, Salhany KE, Wysocka M, Aruga E, Kurzawa H, Chang AE. Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis. J Clin Invest (1998) 101:1441–52.
- Hashimoto W, Osaki T, Okamura H, Robbins PD, Kurimoto M, Nagata S. Differential antitumor effects of administration of recombinant IL-18 or recombinant IL-12 are mediated primarily by Fas-Fas ligand-and perforin-induced tumor apoptosis, respectively. J Immunol (1999) 163:583–9.
- Yoshimoto T, Takeda K, Tanaka T, Ohkusu K, Kashiwamura S-i, Okamura H. IL-12 up-regulates IL-18 receptor expression on T cells, Th1 cells, and B cells: synergism with IL-18 for IFN-γ production. J Immunol (1998) 161:3400–7.
- Müller J-M, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M. Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses. J Immunother (2011) 34:58–64.
- Mählmann K, Feige K, Juhls C, Endmann A, Schuberth H-J, Oswald D. Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma. BMC Vet Res (2015) 11:107.
- Heinzerling LM, Feige K, Rieder S, Akens MK, Dummer R, Stranzinger G. Tumor regression induced by intratumoral injection of DNA coding for human interleukin 12 into melanoma metastases in gray horses. J Mol Med (2001) 78:692–02.
- Greenberg CB, Javsicas LH, Clauson RM, Suckow MA, Kalinauskas AE, Lucroy MD. Field safety experience with an autologous cancer vaccine in 41 horses: a retrospective study (2019–2021). J Equine Vet (2022) 114:103948.
- Brown EL, Ramiya VK, Wright CA, Jerald MM, Via AD, Kuppala VN. Treatment of metastatic equine melanoma with a plasmid DNA vaccine encoding streptococcus pyogenes EMM55 protein. J Equine Vet (2014) 34:704–8.
- Lembcke LM, Kania SA, Blackford JT, Trent DJ, Odoi A, Grosenbaugh DA. Development of immunologic assays to measure response in horses vaccinated with xenogeneic plasmid DNA encoding human tyrosinase. J Equine Vet (2012) 32:607–15.
- Phillips JC, Lembcke LM. Equine melanocytic tumors. Vet Clin Equine Pract (2013) 29:673–87.
- Ottnod J, Smedley R, Walshaw R, Hauptman J, Kiupel M, Obradovich J. A retrospective analysis of the efficacy of Oncept vaccine for the adjunct treatment of canine oral malignant melanoma. Vet Comp Oncol (2013) 11:219–29.
- Pellin MA. The use of Oncept melanoma vaccine in veterinary patients: a review of the literature. Vet Sci (2022) 9:597.
- Tamzali Y, Borde L, Rols M, Golzio M, Lyazrhi F, Teissie J. Successful treatment of equine sarcoids with cisplatin electrochemotherapy: a retrospective study of 48 cases. Equine Vet J (2012) 44:214–20.
- Tozon N, Kramaric P, Kos Kadunc V, Sersa G, Cemazar M. Electrochemotherapy as a single treatment or adjuvant treatment to surgery of cutaneous sarcoid tumours in horses: a 31-case retrospective study. Vet Rec (2016) 179:627.
- Byron CR, DeWitt MR, Latouche EL, Davalos RV, Robertson JL. Treatment of infiltrative superficial tumors in awake standing horses using novel high-frequency pulsed electrical fields. Front Vet Sci (2019) 6:265.
- Geboers B, Scheffer HJ, Graybill PM, Ruarus AH, Nieuwenhuizen S, Puijk RS. High-voltage electrical pulses in oncology: irreversible electroporation, electrochemotherapy, gene electrotransfer, electrofusion, and electroimmunotherapy. Radiology (2020) 295:254–72.
- Gehl J, Skovsgaard T, Mir LM. Vascular reactions to in vivo electroporation: characterization and consequences for drug and gene delivery. Biochimica et Biophysica Acta (BBA)-General Subjects (2002) 1569:51–8.
- Calvet CY, Famin D, André FM, Mir LM. Electrochemotherapy with bleomycin induces hallmarks of immunogenic cell death in murine colon cancer cells. Onco Targets Ther (2014) 3:e28131.
- Ursic K, Kos S, Kamensek U, Cemazar M, Scancar J, Bucek S. Comparable effectiveness and immunomodulatory actions of oxaliplatin and cisplatin in electrochemotherapy of murine melanoma. Bioelectrochemistry (2018) 119:161–71.
- Bendix MB, Houston A, Forde PF, Brint E. Electrochemotherapy and immune interactions; a boost to the system?. Eur J Surg Oncol (2022) 48:1895–00.
- Spugnini EP, Baldi A. Electrochemotherapy in veterinary oncology: state-of-the-art and perspectives. Vet Clin Small Anim Pract (2019) 49:967–79.
- Spugnini EP, Baldi A. Electrochemotherapy in veterinary oncology: from rescue to first line therapy. Electro Protoc (2014) 1121:247–56.
- Davalos RV, Rubinsky B, Mir LM. Theoretical analysis of the thermal effects during in vivo tissue electroporation. Bioelectrochemistry (2003) 61:99–07.
- Kourounis G, Tabet PP, Moris D, Papalambros A, Felekouras E, Georgiades F. Irreversible electroporation (Nanoknife® treatment) in the field of hepatobiliary surgery: current status and future perspectives. J BU ON Off J Balkan Union Oncol (2017) 22:141–9.
- Rossmeisl JH, Garcia PA, Pancotto TE, Robertson JL, Henao-Guerrero N, Neal RE. Safety and feasibility of the NanoKnife system for irreversible electroporation ablative treatment of canine spontaneous intracranial gliomas. J Neurosurg (2015) 123:1008–25.
- Neal RE, II, Rossmeisl JH, Jr, Garcia PA, Lanz OI, Henao-Guerrero N, Davalos RV. Successful treatment of a large soft tissue sarcoma with irreversible electroporation. J Clin Oncol (2011) 29:E372–e377.
- Vroomen L, Petre EN, Cornelis FH, Solomon SB, Srimathveeravalli G. Irreversible electroporation and thermal ablation of tumors in the liver, lung, kidney and bone: what are the differences?. Diagn Interv Imaging (2017) 98:609–17.
- Martin RC, 2nd, Kwon D, Chalikonda S, Sellers M, Kotz E, Scoggins C. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg (2015) 262:486–94.
- Fusco R, Di Bernardo E, D'Alessio V, Salati S, Cadossi M. Reduction of muscle contraction and pain in electroporation-based treatments: an overview. World J Clin Oncol (2021) 12:367–81.
- Sano MB, Fan RE, Cheng K, Saenz Y, Sonn GA, Hwang GL. Reduction of muscle contractions during irreversible electroporation therapy using high frequency bursts of alternating polarity pulses: a laboratory investigation in an ex vivo swine model. J Vasc Interv Radiol (2017) 29:893–898.e4.
- Martin RC, Schwartz E, Adams J, Farah I, Derhake BM. Intra - operative anesthesia Management in Patients Undergoing Surgical Irreversible Electroporation of the pancreas, liver, kidney, and retroperitoneal tumors. Anesthesiol Pain Med (2015) 5:e22786.
- Deodhar A, Dickfeld T, Single GW, Hamilton WC, Jr, Thornton RH, Sofocleous CT. Irreversible electroporation near the heart: ventricular arrhythmias can be prevented with ECG synchronization. Am J Roentgenol (2011) 196:W330–5.
- Senior JM. Morbidity, mortality, and risk of general anesthesia in horses. Vet Clin Equine Pract (2013) 29:1–18.
- O’Donovan KA, Aarnes TK, Hubbell JA, Parker EM, Mollenkopf D, Lerche P. Risk of anesthesia-related complications in draft horses: a retrospective, single-center analysis. Vet Anaesth Analg (2023) 50:157–62.
- Johnston G, Eastment J, Taylor P, Wood J. Is isoflurane safer than halothane in equine anaesthesia? Results from a prospective multicentre randomised controlled trial. Equine Vet J (2004) 36:64–71.
- Johnston G, Eastment J, Wood J, Taylor P. The confidential enquiry into perioperative equine fatalities (CEPEF): mortality results of phases 1 and 2. Vet Anaesth Analg (2002) 29:159–70.
- Bidwell LA, Bramlage LR, Rood WA. Equine perioperative fatalities associated with general anaesthesia at a private practice–a retrospective case series. Vet Anaesth Analg (2007) 34:23–30.
- Young S, Taylor PM. Factors influencing the outcome of equine anaesthesia: a review of 1,314 cases. Equine Vet J (1993) 25:147–51.
- Arena CB, Sano MB, Rossmeisl JH, Caldwell JL, Garcia PA, Rylander MN. High-frequency irreversible electroporation (H-FIRE) for non-thermal ablation without muscle contraction. Biomed Eng Online (2011) 10:1–21.
- Kaufman JD, Fesmire CC, Petrella RA, Fogle CA, Xing L, Gerber D. High-frequency irreversible electroporation using 5,000-V waveforms to create reproducible 2-and 4-cm ablation zones—a laboratory investigation using mechanically perfused liver. J Vasc Interv Radiol (2019) 31:162–168.e7.
- Sano MB, Arena CB, Bittleman KR, DeWitt MR, Cho HJ, Szot CS. Bursts of bipolar microsecond pulses inhibit tumor growth. Sci Rep (2015) 5:14999.
- Sano MB, Arena CB, DeWitt MR, Saur D, Davalos RV. In-vitro bipolar nano- and microsecond electro-pulse bursts for irreversible electroporation therapies. Bioelectrochemistry (2014) 100:69–79.
- Fesmire CC, Petrella RA, Kaufman JD, Topasna N, Sano MB. Irreversible electroporation is a thermally mediated ablation modality for pulses on the order of one microsecond. Bioelectrochemistry (2020) 135:107544.
- Sano MB, Fesmire CC, DeWitt MR, Xing L. Burst and continuous high frequency irreversible electroporation protocols evaluated in a 3D tumor model. Phys Med Biol (2018) 63:135022.
- Petrella RA, Fesmire CC, Kaufman JD, Topasna N, Sano MB. Algorithmically controlled electroporation: a technique for closed loop temperature regulated pulsed electric field Cancer ablation. IEEE Trans Biomed Eng (2020) 67:2176–86.
- Sano MB, Petrella RA, Kaufman JD, Fesmire CC, Xing L, Gerber D. Electro-thermal therapy: microsecond duration pulsed electric field tissue ablation with dynamic temperature control algorithms. Comput Biol Med (2020) 121:103807.
- Sano MB, Fesmire CC, Petrella RA. Electro-thermal therapy algorithms and active internal electrode cooling reduce thermal injury in high frequency pulsed electric field Cancer therapies. Ann Biomed Eng (2021) 49:191–02.
- Fesmire CC, Petrella RA, Fogle CA, Gerber DA, Xing L, Sano MB. Temperature dependence of high frequency irreversible electroporation evaluated in a 3D tumor model. Ann Biomed Eng (2020) 48:2233–46.
- Hasgall PA, Di Gennaro F, Baumgartner C, Neufeld E, Lloyd B, Gosselin MC. IT’IS database for thermal and electromagnetic parameters of biological tissues, version 4.0. IT’IS (2018).
- Arena CB, Garcia PA, Sano MB, Olson JD, Rogers-Cotrone T, Rossmeisl JH, Jr. Focal blood-brain-barrier disruption with high-frequency pulsed electric fields. Technology (2014) 2:206–13.
- Garcia PA, Neal RE, Ellis TL, Olson JD, Henao-Guerrero N. Intracranial nonthermal irreversible electroporation: in vivo analysis. J Membr Biol (2010) 236:127–36.
- Yi Z, Gao Y, Yu F, Zhu Y, Liu H, Li J. Interventions for treatment of cutaneous melanoma in horses: a structured literature review. Vet Res Commun (2023) 47:347–60.
- Robinson EP, Natalini CC. Epidural anesthesia and analgesia in horses. Vet Clin Equine Pract (2002) 18:61–82, vi.
- Spugnini EP, D'Alterio GL, Dotsinsky I, Mudrov T, Dragonetti E, Murace R. Electrochemotherapy for the treatment of multiple melanomas in a horse. J Equine Vet (2011) 31:430–3.
- Rogers WR, Merritt JH, Comeaux JA, Jr, Kuhnel CT, Moreland DF, Teltschik DG. Strength-duration curve for an electrically excitable tissue extended down to near 1 nanosecond. IEEE Trans Plasma Sci (2004) 32:1587–99.
- Garcia PA, Neal RE, Sano MB, Robertson JL, Davalos RV. An experimental investigation of temperature changes during electroporation. 2011 XXXth URSI General Assembly and Scientific Symposium (2011).
- Garcia PA, Arena CB, Neal RE, Goldberg SN, Ben-David E, Davalos RV. Adapting the Cassini Curve to Approximate In Vivo Irreversible Electroporation Ablations in Porcine Liver. ASME 2013 Summer Bioengineering Conference (2013).
- Fesmire CC, Williamson RH, Petrella RA, Kaufman JD, Topasna N, Sano MB. Integrated time nanosecond pulse irreversible electroporation (INSPIRE): assessment of dose, temperature, and voltage on experimental and clinical treatment outcomes. IEEE Trans Biomed Eng (2023):1–10.
- Sano MB, DeWitt MR, Teeter SD, Xing L. Optimization of a single insertion electrode array for the creation of clinically relevant ablations using high-frequency irreversible electroporation. Comput Biol Med (2018) 95:107–17.
- Sano MB, Fan RE, Hwang GL, Sonn GA, Xing L. Production of spherical ablations using nonthermal irreversible electroporation: a laboratory investigation using a Single electrode and grounding pad. J Vasc Intervent Radiol JVIR (2016) 27:1432–1440.e3.
- Tremble LF, O'Brien MA, Soden DM, Forde PF. Electrochemotherapy with cisplatin increases survival and induces immunogenic responses in murine models of lung cancer and colorectal cancer. Cancer Lett (2019) 442:475–82.
- He C, Huang X, Zhang Y, Lin X, Li S. T-cell activation and immune memory enhancement induced by irreversible electroporation in pancreatic cancer. Clin Transl Med (2020) 10:e39.
- Dai Z, Wang Z, Lei K, Liao J, Peng Z, Lin M. Irreversible electroporation induces CD8+ T cell immune response against post-ablation hepatocellular carcinoma growth. Cancer Lett (2021) 503:1–10.
- Justesen TF, Orhan A, Raskov H, Nolsoe C, Gögenur I. Electroporation and immunotherapy—unleashing the abscopal effect. Cancers (2022) 14:2876.
- Brock RM, Beitel-White N, Davalos RV, Allen IC. Starting a Fire without flame: the induction of cell death and inflammation in electroporation-based tumor ablation strategies. Front Oncol (2020) 10:1235.
- Edelblute CM, Hornef J, Burcus NI, Norman T, Beebe SJ, Schoenbach K. Controllable moderate heating enhances the therapeutic efficacy of irreversible electroporation for pancreatic Cancer. Sci Rep (2017) 7:11767.
- Zhao J, Wen X, Tian L, Li T, Xu C, Wen X. Irreversible electroporation reverses resistance to immune checkpoint blockade in pancreatic cancer. Nat Commun (2019) 10:899.
- Ganbaatar O, Konnai S, Okagawa T, Nojima Y, Maekawa N, Minato E. PD-L1 expression in equine malignant melanoma and functional effects of PD-L1 blockade. PLoS One (2020) 15:e0234218.
- Porcellato I, Mecocci S, Brachelente C, Cappelli K, Armando F, Tognoloni A. PD-L1/PD-1 and CTLA-4 expression in equine penile squamous cell carcinomas. Animals (2021) 11:2121.
- Benvegnen J, De Breuyn B, Gerber V, Rottenberg S, Koch C. Immunohistochemical analysis of programmed death-ligand 1 expression in equine sarcoids. J Equine Vet (2021) 97:103338.
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists