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Animals : an open access journal from MDPI2021; 11(11); 3250; doi: 10.3390/ani11113250

Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses.

Abstract: The naturally occurring betulinic acid (BA) and its derivative NVX-207 induce apoptosis in equine melanoma cells in vitro. After topical application, high concentrations of the substances can be reached in healthy equine skin. With the aim to investigate the effect and safety of topically applied BA and NVX-207 in horses with melanocytic tumors, the longitudinal, prospective, randomized, double-blind, placebo-controlled study protocol included eighteen Lipizzaner mares with early-stage cutaneous melanoma assigned to three groups. Melanocytic lesions were topically treated either with a placebo, 1% BA or 1% NVX-207 twice a day for 91 days. Caliper measurements, clinical examinations and blood tests were performed to assess the effects and safety of the medication. The topical treatment was convenient and safe. The volumes of tumors treated with BA were significantly reduced over time as compared to tumors treated with the placebo from day 80 of the study. Although treatment with NVX-207 seemed to decrease tumor volume, these results did not reach statistical significance. The findings must be regarded as preliminary due to the limited group size and need to be replicated in a larger cohort with modified pharmaceutical test formulations. Accordingly, the treatment protocol cannot yet be recommended in its current form.
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Publication Date: 2021-11-13 PubMed ID: 34827981PubMed Central: PMC8614291DOI: 10.3390/ani11113250Google Scholar: Lookup
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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 examines the impacts of applying betulinic acid (BA) and its derivative NVX-207 topically on horses with melanocytic tumors. The study found that BA significantly reduced the volume of tumors over time, while the effects of NVX-207 were not statistically significant.

Overview of the Research

  • The research focuses on testing the effectiveness and safety of topically applied betulinic acid (BA) and its derivative NVX-207 in treating melanocytic tumors in horses.
  • The substances, BA and NVX-207, have been identified to induce apoptosis, or cell death, in equine melanoma cells in vitro, meaning under a controlled laboratory environment.
  • However, this research attempts to study their effects in a real-world scenario where these substances are applied topically to the skin of horses.

Research Methodology

  • The study included eighteen Lipizzaner mares with early-stage cutaneous melanoma, making it a specific and controlled study group.
  • These horses were divided into three groups and were treated with a placebo, 1% BA or 1% NVX-207 applied twice daily for a period of 91 days.
  • The study was longitudinal, meaning it studied the same subjects over this protracted period.
  • The research is also described as prospective, randomized, double-blind, and placebo-controlled, indicating a high level of scientific rigor and control over variables.

Findings of the Study

  • The topical treatment of melanocytic lesions with BA and NVX-207 was found to be convenient and safe, indicating no severe side effects or practical difficulties.
  • The volumes of tumors treated with BA significantly reduced over time when compared to those treated with a placebo from the 80th day of the study onwards.
  • The treatment with NVX-207 seemed to decrease tumor volume but the results were not statistically significant, suggesting that the difference could be due to chance rather than the treatment itself.

Limitations and Recommendations

  • While the findings are promising, they are considered preliminary due to the limited size of the test group.
  • Replication of the study in a larger cohort and with modified pharmaceutical test formulations is recommended to validate and refine the findings.
  • The current form of the treatment protocol, therefore, cannot yet be recommended, indicating further research is needed before such treatments can become standard practice.

Cite This Article

APA
Weber LA, Delarocque J, Feige K, Kietzmann M, Kalbitz J, Meißner J, Paschke R, Cavalleri JV. (2021). Effects of Topically Applied Betulinic Acid and NVX-207 on Melanocytic Tumors in 18 Horses. Animals (Basel), 11(11), 3250. https://doi.org/10.3390/ani11113250

Publication

Animals : an open access journal from MDPI
ISSN: 2076-2615
NlmUniqueID: 101635614
Country: Switzerland
Language: English
Volume: 11
Issue: 11
PII: 3250

Researcher Affiliations

Weber, Lisa A
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany.
Delarocque, Julien
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany.
Feige, Karsten
  • Clinic for Horses, University of Veterinary Medicine Hannover, Foundation, Bünteweg 9, 30559 Hannover, Germany.
Kietzmann, Manfred
  • Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany.
Kalbitz, Jutta
  • Biosolutions Halle GmbH, Weinbergweg 22, 06120 Halle (Saale), Germany.
Meißner, Jessica
  • Department of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Foundation, Bünteweg 17, 30559 Hannover, Germany.
Paschke, Reinhard
  • Biozentrum, Martin-Luther-University Halle-Wittenberg, Weinbergweg 22, 06120 Halle (Saale), Germany.
Cavalleri, Jessika-M V
  • Equine Internal Medicine, University Equine Clinic, University of Veterinary Medicine Vienna, Veterinärplatz 1, 1210 Vienna, Austria.

Grant Funding

  • 16KN051526 BMWI / Central Innovation Program of the German Federal Ministry for Economic Affairs and Energy

Conflict of Interest Statement

The authors declare no conflict of interest.

References

This article includes 70 references
  1. Sundström E, Imsland F, Mikko S, Wade C, Sigurdsson S, Pielberg GR, Golovko A, Curik I, Seltenhammer MH, Sölkner J, Lindblad-Toh K, Andersson L. Copy number expansion of the STX17 duplication in melanoma tissue from Grey horses.. BMC Genomics 2012 Aug 2;13:365.
    doi: 10.1186/1471-2164-13-365pmc: PMC3443021pubmed: 22857264google scholar: lookup
  2. Rosengren Pielberg G, Golovko A, Sundström E, Curik I, Lennartsson J, Seltenhammer MH, Druml T, Binns M, Fitzsimmons C, Lindgren G, Sandberg K, Baumung R, Vetterlein M, Strömberg S, Grabherr M, Wade C, Lindblad-Toh K, Pontén F, Heldin CH, Sölkner J, Andersson L. A cis-acting regulatory mutation causes premature hair graying and susceptibility to melanoma in the horse.. Nat Genet 2008 Aug;40(8):1004-9.
    doi: 10.1038/ng.185pubmed: 18641652google scholar: lookup
  3. Seltenhammer MH, Simhofer H, Scherzer S, Zechner R, Curik I, Sölkner J, Brandt SM, Jansen B, Pehamberger H, Eisenmenger E. Equine melanoma in a population of 296 grey Lipizzaner horses.. Equine Vet J 2003 Mar;35(2):153-7.
    doi: 10.2746/042516403776114234pubmed: 12638791google scholar: lookup
  4. Fleury C, Bérard F, Balme B, Thomas L. The study of cutaneous melanomas in Camargue-type gray-skinned horses (1): clinical-pathological characterization.. Pigment Cell Res 2000 Feb;13(1):39-46.
    doi: 10.1034/j.1600-0749.2000.130108.xpubmed: 10761995google scholar: lookup
  5. Seltenhammer MH, Heere-Ress E, Brandt S, Druml T, Jansen B, Pehamberger H, Niebauer GW. Comparative histopathology of grey-horse-melanoma and human malignant melanoma.. Pigment Cell Res 2004 Dec;17(6):674-81.
    doi: 10.1111/j.1600-0749.2004.00192.xpubmed: 15541026google scholar: lookup
  6. Sutton R.H., Coleman G.T.. Melanoma and the greying horse.. RIRDC Res. Pap. Ser. 1997;97:1–27.
  7. Johnson PJ. Dermatologic tumors (excluding sarcoids).. Vet Clin North Am Equine Pract 1998 Dec;14(3):625-58, viii.
    doi: 10.1016/S0749-0739(17)30190-6pubmed: 9891728google scholar: lookup
  8. MacGillivray KC, Sweeney RW, Del Piero F. Metastatic melanoma in horses.. J Vet Intern Med 2002 Jul-Aug;16(4):452-6.
    doi: 10.1111/j.1939-1676.2002.tb01264.xpubmed: 12141308google scholar: lookup
  9. Moore J.S., Shaw C., Shaw E., Buechner-Maxwell V., Scarratt W., Crisman M.V., Furr M., Robertson J.L.. Melanoma in horses: Current perspectives.. Equine Vet. Educ. 2013;25:144–151.
    doi: 10.1111/j.2042-3292.2011.00368.xgoogle scholar: lookup
  10. Patterson-Kane JC, Sanchez LC, Uhl EW, Edens LM. Disseminated metastatic intramedullary melanoma in an aged grey horse.. J Comp Pathol 2001 Aug-Oct;125(2-3):204-7.
    doi: 10.1053/jcpa.2001.0481pubmed: 11578137google scholar: lookup
  11. Smith SH, Goldschmidt MH, McManus PM. A comparative review of melanocytic neoplasms.. Vet Pathol 2002 Nov;39(6):651-78.
    doi: 10.1354/vp.39-6-651pubmed: 12450197google scholar: lookup
  12. Rodríguez F, Forga J, Herráez P, Andrada M, Fernández A. Metastatic melanoma causing spinal cord compression in a horse.. Vet Rec 1998 Mar 7;142(10):248-9.
    doi: 10.1136/vr.142.10.248pubmed: 9549868google scholar: lookup
  13. Myrna K., Sheridan C.. Melanocytic ocular and periocular tumours of the horse.. Equine Vet. Educ. 2019;31:410–412.
    doi: 10.1111/eve.12847google scholar: lookup
  14. MacKay RJ. Treatment Options for Melanoma of Gray Horses.. Vet Clin North Am Equine Pract 2019 Aug;35(2):311-325.
    doi: 10.1016/j.cveq.2019.04.003pubmed: 31279435google scholar: lookup
  15. Luís A., Ruela M., Perissinato A.G., Esselin M., Lino D.S.. Evaluation of skin absorption of drugs from topical and transdermal formulations.. Braz. J. Pharm. Sci. 2016;52:527–544.
    doi: 10.1590/S1984-82502016000300018google scholar: lookup
  16. Prausnitz M.R., Elias P.M., Franz T.J., Schmuth M., Tsai J.-C., Menon G.K.. Skin Barrier and Transdermal Drug Delivery.. Med. Ther. 2012;5:2065–2073.
  17. Fulda S. Betulinic Acid for cancer treatment and prevention.. Int J Mol Sci 2008 Jun;9(6):1096-1107.
    doi: 10.3390/ijms9061096pmc: PMC2658785pubmed: 19325847google scholar: lookup
  18. Sarek J., Kvasnica M., Vlk M., Urban M., Dzubak P., Hajduch M.. The Potential of Triterpenoids in the Treatment of Melanoma, Research on Melanoma—A Glimpse into Current Directions and Future Trends.. InTech Rijeka, Croatia: 2011.
    doi: 10.5772/57353google scholar: lookup
  19. Ríos JL, Máñez S. New Pharmacological Opportunities for Betulinic Acid.. Planta Med 2018 Jan;84(1):8-19.
    doi: 10.1055/s-0043-123472pubmed: 29202513google scholar: lookup
  20. Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CW, Fong HH, Kinghorn AD, Brown DM. Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis.. Nat Med 1995 Oct;1(10):1046-51.
    doi: 10.1038/nm1095-1046pubmed: 7489361google scholar: lookup
  21. Ali-Seyed M, Jantan I, Vijayaraghavan K, Bukhari SN. Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy.. Chem Biol Drug Des 2016 Apr;87(4):517-36.
    doi: 10.1111/cbdd.12682pubmed: 26535952google scholar: lookup
  22. Fulda S, Kroemer G. Targeting mitochondrial apoptosis by betulinic acid in human cancers.. Drug Discov Today 2009 Sep;14(17-18):885-90.
    doi: 10.1016/j.drudis.2009.05.015pubmed: 19520182google scholar: lookup
  23. Yang C, Li Y, Fu L, Jiang T, Meng F. Betulinic acid induces apoptosis and inhibits metastasis of human renal carcinoma cells in vitro and in vivo.. J Cell Biochem 2018 Nov;119(10):8611-8622.
    doi: 10.1002/jcb.27116pubmed: 29923216google scholar: lookup
  24. Chowdhury AR, Mandal S, Mittra B, Sharma S, Mukhopadhyay S, Majumder HK. Betulinic acid, a potent inhibitor of eukaryotic topoisomerase I: identification of the inhibitory step, the major functional group responsible and development of more potent derivatives.. Med Sci Monit 2002 Jul;8(7):BR254-65.
    pubmed: 12118187
  25. Dillon LW, Pierce LC, Lehman CE, Nikiforov YE, Wang YH. DNA topoisomerases participate in fragility of the oncogene RET.. PLoS One 2013;8(9):e75741.
    doi: 10.1371/journal.pone.0075741pmc: PMC3770543pubmed: 24040417google scholar: lookup
  26. Ganguly A, Das B, Roy A, Sen N, Dasgupta SB, Mukhopadhayay S, Majumder HK. Betulinic acid, a catalytic inhibitor of topoisomerase I, inhibits reactive oxygen species-mediated apoptotic topoisomerase I-DNA cleavable complex formation in prostate cancer cells but does not affect the process of cell death.. Cancer Res 2007 Dec 15;67(24):11848-58.
    doi: 10.1158/0008-5472.CAN-07-1615pubmed: 18089815google scholar: lookup
  27. Karna E, Szoka L, Palka JA. Betulinic acid inhibits the expression of hypoxia-inducible factor 1alpha and vascular endothelial growth factor in human endometrial adenocarcinoma cells.. Mol Cell Biochem 2010 Jul;340(1-2):15-20.
    doi: 10.1007/s11010-010-0395-8pubmed: 20174965google scholar: lookup
  28. Ren W., Qin L., Xu Y., Cheng N.. Inhibition of betulinic acid to growth and angiogenesis of human colorectal cancer cell in nude mice.. Chin.-German J. Clin. Oncol. 2010;9:153–157.
    doi: 10.1007/s10330-010-0002-1google scholar: lookup
  29. Melzig MF, Bormann H. Betulinic acid inhibits aminopeptidase N activity.. Planta Med 1998 Oct;64(7):655-7.
    doi: 10.1055/s-2006-957542pubmed: 9810272google scholar: lookup
  30. Kwon HJ, Shim JS, Kim JH, Cho HY, Yum YN, Kim SH, Yu J. Betulinic acid inhibits growth factor-induced in vitro angiogenesis via the modulation of mitochondrial function in endothelial cells.. Jpn J Cancer Res 2002 Apr;93(4):417-25.
    doi: 10.1111/j.1349-7006.2002.tb01273.xpmc: PMC5927016pubmed: 11985792google scholar: lookup
  31. Willmann M, Wacheck V, Buckley J, Nagy K, Thalhammer J, Paschke R, Triche T, Jansen B, Selzer E. Characterization of NVX-207, a novel betulinic acid-derived anti-cancer compound.. Eur J Clin Invest 2009 May;39(5):384-94.
    doi: 10.1111/j.1365-2362.2009.02105.xpubmed: 19309323google scholar: lookup
  32. Csuk R. Betulinic acid and its derivatives: a patent review (2008-2013).. Expert Opin Ther Pat 2014 Aug;24(8):913-23.
    doi: 10.1517/13543776.2014.927441pubmed: 24909232google scholar: lookup
  33. Liebscher G, Vanchangiri K, Mueller T, Feige K, Cavalleri JM, Paschke R. In vitro anticancer activity of Betulinic acid and derivatives thereof on equine melanoma cell lines from grey horses and in vivo safety assessment of the compound NVX-207 in two horses.. Chem Biol Interact 2016 Feb 25;246:20-9.
    doi: 10.1016/j.cbi.2016.01.002pubmed: 26772157google scholar: lookup
  34. Weber LA, Meißner J, Delarocque J, Kalbitz J, Feige K, Kietzmann M, Michaelis A, Paschke R, Michael J, Pratscher B, Cavalleri JV. Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro.. BMC Vet Res 2020 Feb 5;16(1):44.
    doi: 10.1186/s12917-020-2262-5pmc: PMC7003431pubmed: 32024502google scholar: lookup
  35. Weber LA, Funtan A, Paschke R, Delarocque J, Kalbitz J, Meißner J, Feige K, Kietzmann M, Cavalleri JV. In vitro assessment of triterpenoids NVX-207 and betulinyl-bis-sulfamate as a topical treatment for equine skin cancer.. PLoS One 2020;15(11):e0241448.
    doi: 10.1371/journal.pone.0241448pmc: PMC7643960pubmed: 33151949google scholar: lookup
  36. Weber LA, Puff C, Kalbitz J, Kietzmann M, Feige K, Bosse K, Rohn K, Cavalleri JV. Concentration profiles and safety of topically applied betulinic acid and NVX-207 in eight healthy horses-A randomized, blinded, placebo-controlled, crossover pilot study.. J Vet Pharmacol Ther 2021 Jan;44(1):47-57.
    doi: 10.1111/jvp.12903pubmed: 32845519google scholar: lookup
  37. Faul F, Erdfelder E, Lang AG, Buchner A. G*Power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences.. Behav Res Methods 2007 May;39(2):175-91.
    doi: 10.3758/BF03193146pubmed: 17695343google scholar: lookup
  38. Kienzle E., Schramme S.C.. Body Condition Scoring and prediction of body weight in adult Warm blooded horses.. Pferdeheilkunde Equine Med. 2004;20:517–524.
    doi: 10.21836/PEM20040604google scholar: lookup
  39. Mählmann K, Feige K, Juhls C, Endmann A, Schuberth HJ, Oswald D, Hellige M, Doherr M, Cavalleri JM. Local and systemic effect of transfection-reagent formulated DNA vectors on equine melanoma.. BMC Vet Res 2015 Jun 11;11:132.
    doi: 10.1186/s12917-015-0422-9pmc: PMC4464139pubmed: 26063232google scholar: lookup
  40. Faustino-Rocha A, Oliveira PA, Pinho-Oliveira J, Teixeira-Guedes C, Soares-Maia R, da Costa RG, Colaço B, Pires MJ, Colaço J, Ferreira R, Ginja M. Estimation of rat mammary tumor volume using caliper and ultrasonography measurements.. Lab Anim (NY) 2013 Jun;42(6):217-24.
    doi: 10.1038/laban.254pubmed: 23689461google scholar: lookup
  41. R Core Team. A Language and Environment for Statistical Computing.. R Foundation for Statistical Computing Vienna, Austria: 2013.
  42. Wood S.N.. Generalized Additive Models: An Introduction with R.. 2nd ed. Chapman and Hall/CRC; Boca Raton, FL, USA: 2017.
  43. Wood S.. Thin plate regression splines.. J. R. Stat. Soc. Ser. B Stat. Methodol. 2003;65:95–114.
    doi: 10.1111/1467-9868.00374google scholar: lookup
  44. Rose N.L., Yang H., Turner S., Simpson G.. An assessment of the mechanisms for the transfer of lead and mercury from atmospherically contaminated organic soils to lake sediments with particular reference to Scotland, UK.. Geochim. Cosmochim. Acta. 2012;82:113–135.
    doi: 10.1016/j.gca.2010.12.026google scholar: lookup
  45. Scott D.. Neoplastic Diseases.. Large Anim, Dermatology 1988. pp. 448–452.
  46. Kapałczyńska M, Kolenda T, Przybyła W, Zajączkowska M, Teresiak A, Filas V, Ibbs M, Bliźniak R, Łuczewski Ł, Lamperska K. 2D and 3D cell cultures - a comparison of different types of cancer cell cultures.. Arch Med Sci 2018 Jun;14(4):910-919.
    doi: 10.5114/aoms.2016.63743pmc: PMC6040128pubmed: 30002710google scholar: lookup
  47. Adega F., Chaves R.. Oncogenomics and Cancer Proteomics-Novel Approaches in Biomarkers Discovery and Therapeutic Targets in Cancer.. IntechOpen London, UK: 2013. The Importance of Cancer Cell Lines as in vitro Models in Cancer Methylome Analysis and Anticancer Drugs Testing; pp. 139–166.
    doi: 10.5772/53110google scholar: lookup
  48. Jain RK, Martin JD, Stylianopoulos T. The role of mechanical forces in tumor growth and therapy.. Annu Rev Biomed Eng 2014 Jul 11;16:321-46.
    doi: 10.1146/annurev-bioeng-071813-105259pmc: PMC4109025pubmed: 25014786google scholar: lookup
  49. Peckary R.. Average Growth of Melanomas in Lipizzaner Horses and First Test Series for the Development of an ELISA for Detection of Antibodies Directed against Human Tyrosinase in with Human Tyrosinase Vaccinated Horses.. University of Veterinary Medicine Vienna; Vienna, Austria: 2019.
  50. Müller J, Feige K, Wunderlin P, Hödl A, Meli ML, Seltenhammer M, Grest P, Nicolson L, Schelling C, Heinzerling LM. 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 Jan;34(1):58-64.
    doi: 10.1097/CJI.0b013e3181fe1997pubmed: 21150713google scholar: lookup
  51. Azimi F, Scolyer RA, Rumcheva P, Moncrieff M, Murali R, McCarthy SW, Saw RP, Thompson JF. Tumor-infiltrating lymphocyte grade is an independent predictor of sentinel lymph node status and survival in patients with cutaneous melanoma.. J Clin Oncol 2012 Jul 20;30(21):2678-83.
    doi: 10.1200/JCO.2011.37.8539pubmed: 22711850google scholar: lookup
  52. Fu Q, Chen N, Ge C, Li R, Li Z, Zeng B, Li C, Wang Y, Xue Y, Song X, Li H, Li G. Prognostic value of tumor-infiltrating lymphocytes in melanoma: a systematic review and meta-analysis.. Oncoimmunology 2019;8(7):1593806.
    doi: 10.1080/2162402X.2019.1593806pmc: PMC6527267pubmed: 31143514google scholar: lookup
  53. Haspeslagh M, Jordana Garcia M, Vlaminck LEM, Martens AM. Topical use of 5% acyclovir cream for the treatment of occult and verrucous equine sarcoids: a double-blinded placebo-controlled study.. BMC Vet Res 2017 Oct 6;13(1):296.
    doi: 10.1186/s12917-017-1215-0pmc: PMC6389201pubmed: 28985733google scholar: lookup
  54. Stadler S, Kainzbauer C, Haralambus R, Brehm W, Hainisch E, Brandt S. Successful treatment of equine sarcoids by topical aciclovir application.. Vet Rec 2011 Feb 19;168(7):187.
    doi: 10.1136/vr.c5430pubmed: 21493530google scholar: lookup
  55. Nogueira SA, Torres SM, Malone ED, Diaz SF, Jessen C, Gilbert S. Efficacy of imiquimod 5% cream in the treatment of equine sarcoids: a pilot study.. Vet Dermatol 2006 Aug;17(4):259-65.
    doi: 10.1111/j.1365-3164.2006.00526.xpubmed: 16827669google scholar: lookup
  56. Pettersson CM, Broström H, Humblot P, Bergvall KE. Topical treatment of equine sarcoids with imiquimod 5% cream or Sanguinaria canadensis and zinc chloride - an open prospective study.. Vet Dermatol 2020 Dec;31(6):471-e126.
    doi: 10.1111/vde.12900pubmed: 33016520google scholar: lookup
  57. Moore J.S.. A Translational Study Evaluating the Uses of Diagnostic and Therapeutic Practices Established in Human Malig-nant Melanoma in Equine Malignant Melanoma.. Virginia Polytechnic Institute and State University; Blacksburg, VA, USA: 2013.
  58. Scott D.W., Miller W.H.. Equine Dermatology.. 2nd ed. Penny Rudolph; Maryland Heights, MO, USA: 2011.
  59. Galgon T, Wohlrab W, Dräger B. Betulinic acid induces apoptosis in skin cancer cells and differentiation in normal human keratinocytes.. Exp Dermatol 2005 Oct;14(10):736-43.
    doi: 10.1111/j.1600-0625.2005.00352.xpubmed: 16176281google scholar: lookup
  60. Selzer E, Pimentel E, Wacheck V, Schlegel W, Pehamberger H, Jansen B, Kodym R. Effects of betulinic acid alone and in combination with irradiation in human melanoma cells.. J Invest Dermatol 2000 May;114(5):935-40.
    doi: 10.1046/j.1523-1747.2000.00972.xpubmed: 10771474google scholar: lookup
  61. Surowiak P, Drag M, Materna V, Dietel M, Lage H. Betulinic acid exhibits stronger cytotoxic activity on the normal melanocyte NHEM-neo cell line than on drug-resistant and drug-sensitive MeWo melanoma cell lines.. Mol Med Rep 2009 Jul-Aug;2(4):543-8.
    doi: 10.3892/mmr_00000134pubmed: 21475863google scholar: lookup
  62. Rowe EL, Sullins KE. Excision as treatment of dermal melanomatosis in horses: 11 cases (1994-2000).. J Am Vet Med Assoc 2004 Jul 1;225(1):94-6.
    doi: 10.2460/javma.2004.225.94pubmed: 15239480google scholar: lookup
  63. Groom L.M., Sullins K.E.. Surgical excision of large melanocytic tumours in grey horses: 38 cases (2001–2013). Equine Vet. Educ. 2017;30:438–443.
    doi: 10.1111/eve.12767google scholar: lookup
  64. Bradley W.M., Schilpp D., Khatibzadeh S.M.. Electronic brachytherapy used for the successful treatment of three different types of equine tumours.. Equine Vet. Educ. 2017;29:293–298.
    doi: 10.1111/eve.12420google scholar: lookup
  65. Henson F.M.D., Dobson J.M.. Use of radiation therapy in the treatment of equine neoplasia.. Equine Vet. Educ. 2010;16:315–318.
    doi: 10.1111/j.2042-3292.2004.tb00319.xgoogle scholar: lookup
  66. 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 May 15;230(10):1506-13.
    doi: 10.2460/javma.230.10.1506pubmed: 17504043google scholar: lookup
  67. 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 Nov 15;229(10):1617-22.
    doi: 10.2460/javma.229.10.1617pubmed: 17107319google scholar: lookup
  68. Spugnini E.P., Alterio G.L.D., Dotsinsky I., Mudrov T., Dragonetti E., Murace R., Citro G., Baldi A.. Electrochemotherapy for the Treatment of Multiple Melanomas in a Horse.. J. Equine Vet. Sci. 2011;31:430–433.
    doi: 10.1016/j.jevs.2011.01.009google scholar: lookup
  69. Phillips JC, Lembcke LM, Noltenius CE, Newman SJ, Blackford JT, Grosenbaugh DA, Leard AT. Evaluation of tyrosinase expression in canine and equine melanocytic tumors.. Am J Vet Res 2012 Feb;73(2):272-8.
    doi: 10.2460/ajvr.73.2.272pubmed: 22280389google scholar: lookup
  70. Heinzerling LM, Feige K, Rieder S, Akens MK, Dummer R, Stranzinger G, Moelling K. Tumor regression induced by intratumoral injection of DNA coding for human interleukin 12 into melanoma metastases in gray horses.. J Mol Med (Berl) 2001;78(12):692-702.
    doi: 10.1007/s001090000165pubmed: 11434722google scholar: lookup

Citations

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  1. Gielecińska A, Kciuk M, Mujwar S, Celik I, Kołat D, Kałuzińska-Kołat Ż, Kontek R. Substances of Natural Origin in Medicine: Plants vs. Cancer. Cells 2023 Mar 23;12(7).
    doi: 10.3390/cells12070986pubmed: 37048059google scholar: lookup
  2. Pimenta J, Prada J, Cotovio M. Equine Melanocytic Tumors: A Narrative Review. Animals (Basel) 2023 Jan 10;13(2).
    doi: 10.3390/ani13020247pubmed: 36670786google scholar: lookup
  3. Yi Z, Gao Y, Yu F, Zhu Y, Liu H, Li J, Murua Escobar H. Interventions for treatment of cutaneous melanoma in horses: a structured literature review. Vet Res Commun 2023 Jun;47(2):347-360.
    doi: 10.1007/s11259-022-10023-8pubmed: 36329228google scholar: lookup
  4. Ganguly A, Halder A, Healy K, Daugherty S, Kimura S, Banerjee R, Beckel JM, Tyagi P. Metabolic Reprogramming of Urothelial Carcinoma-A Theragnostic Target for Betulinic Acid. Int J Mol Sci 2025 Jun 11;26(12).
    doi: 10.3390/ijms26125598pubmed: 40565062google scholar: lookup
  5. Zscherpe P, Kalbitz J, Weber LA, Paschke R, Mäder K, von Rechenberg B, Cavalleri JV, Meißner J, Klein K. Potent drug delivery enhancement of betulinic acid and NVX-207 into equine skin in vitro - a comparison between a novel oxygen flow-assisted transdermal application device and microemulsion gels. BMC Vet Res 2024 May 16;20(1):202.
    doi: 10.1186/s12917-024-04064-1pubmed: 38755639google scholar: lookup
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