Evaluación del daño en el ADN inducido por quimioterapia metronómica en leucocitos de sangre periférica de pacientes caninos con cáncer de mama mediante el ensayo cometa alcalino
Resumen
El cáncer de mama es una enfermedad que demanda tratamientos efectivos. La quimioterapia convencional, aunque eficaz, con frecuencia ocasiona efectos secundarios perjudiciales. En contraste, la quimioterapia metronómica (mCHT), que implica la administración continua de dosis bajas de fármacos anticancerígenos, se presenta como una alternativa menos agresiva. En este estudio, se evaluó el impacto genotóxico del tratamiento con ciclofosfamida y meloxicam bajo el enfoque de mCHT en diez pacientes caninas (Canis lupus familiaris) con carcinoma mamario después de someterse a mastectomía. Las pacientes se sometieron a evaluaciones mensuales, que incluyeron radiografías de tórax, análisis de sangre y el ensayo cometa alcalino para medir efectos genotóxicos del antineoplásico. Estos resultados se compararon con los de un grupo que recibió quimioterapia convencional. Los resultados revelaron que las pacientes sometidas a mCHT experimentaron niveles significativamente menores de daño al ADN en comparación con las que recibieron quimioterapia convencional. Además, se observó una disminución del daño al ADN con el tiempo durante la mCHT, lo que sugiere que las perras podrían haber desarrollado tolerancia al tratamiento. Los parámetros sanguíneos se mantuvieron estables en el grupo tratado con mCHT, y las radiografías no mostraron signos de recurrencia o metástasis. Todas las perras sobrevivieron durante el año de seguimiento sin recurrencia del cáncer de mama. Se concluye que la mCHT con ciclofosfamida parece ser una opción terapéutica poco agresiva con un perfil genotóxico más favorable en el tratamiento del cáncer de mama en perras.
Descargas
Citas
Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. Cancer American (AC) Cancer J. Clin. [Internet]. 2021; 71(3):209–249. doi: https://doi.org/ftxg
Centers for Disease Control (CDC) Breast Cancer. What is breast cancer? Centers for Disease Control and Prevention. [Internet]. 2022 [cited 24 Aug 2023]; p 1-2. Available in: https://goo.su/Lfgfm.
Weigelt, B., Peterse, JL, Van’t Veer, LJ. Breast cancer metastasis: markers and models. Nature Reviews. Cancer. [Internet]. 2005; 5(8). 591–602. doi: https://doi.org/cn845x
Abbas Z, Rehman S. An Overview of Cancer Treatment Modalities. In: Shahzad HN, editor. Neoplasm. [Internet]. London: IntechOpen; 2018. 21 p. doi: https://doi.org/mdkk
Hassan MSU, Ansari J, Spooner D, Hussain SA. Chemotherapy for breast cancer (Review). Oncol. Rep. [Internet]. 2010; 24(5):1121–1131. doi: https://doi.org/fxf66r
Fulda S, Galluzzi L, Kroemer G. Targeting mitochondria for cancer therapy. Nature Reviews. Drug Discovery. [Internet]. 2010; 9(6):447–464. doi: https://doi.org/dfwwsm
Solimini NL, Luo J, Elledge SJ. Non-oncogene addiction and the stress phenotype of cancer cells. Cell. [Internet]. 2007; 130(6):986–988. doi: https://doi.org/c9dx3v
Maiti R. Metronomic chemotherapy. J. Pharmacol. Pharmacotherapeut. [Internet]. 2014; 5(3):186–192. doi: https://doi.org/ghpcq9
Cazzaniga ME, Pinotti G, Montagna E, Amoroso D, Berardi R, Butera A, Cagossi K, Cavanna L, Ciccarese M, Cinieri S, Cretella E, De Conciliis E, Febbraro A, Ferraù F, Ferzi A, Fiorentini G, Fontana A, Gambaro AR, Garrone O, Gebbia V, Generali D, Gianni L, Giovanardi F, Grassadonia A, Leonardi V, Marchetti P, Melegari E, Musolino A, Nicolini M, Putzu C, Riccardi F, Santini D, Saracchini S, Sarobba MG, Schintu MG, Scognamiglio G, Spadaro P, Taverniti C, Toniolo D, Tralongo P, Turletti A, Valenza R, Valerio MR, Vici P, Clivio L, Torri V. Metronomic chemotherapy for advanced breast cancer patients in the real world practice: Final results of the VICTOR-6 study. Breast. 2019; 48:7-16. doi: https://doi.org/mdkm
Bignami M, Casorelli I, Karran P. Mismatch repair and response to DNA-damaging antitumour therapies. Eur. J. Cancer. [Internet]. 2003; 39(15):2142–2149. doi: https://doi.org/frp59m
van den Boogaard WMC, Komninos DSJ, Vermeij WP. Chemotherapy Side-Effects: Not All DNA Damage Is Equal. Cancers. [Internet]. 2022; 14(3):627. doi: https://doi.org/gpszqd
Van Maanen JM, Retèl J, de Vries J, Pinedo HM. Mechanism of action of antitumor drug etoposide: a review. J. Natl. Cancer Inst. [Internet]. 1988; 80(19):1526–1533. doi: https://doi.org/czh43k
Robbins WA. Cytogenetic damage measured in human sperm following cancer chemotherapy. Mutat. Res. [Internet]. 1996; 355(1-2):235–252. doi: https://doi.org/bdjd8s
Li L-Y, Guan YD, Chen XS, Yang JM, Cheng Y. DNA Repair Pathways in Cancer Therapy and Resistance. Front. Pharmacol. [Internet]. 2020; 11:629266. doi: https://doi.org/mdsd
Lu Y, Liu Y, Yang C. Evaluating In Vitro DNA Damage Using Comet Assay. J Vis Exp. [Internet]. 2017; (128):e56450. doi: https://doi.org/gs5z2v
McKelvey-Martin VJ, Green MH, Schmezer P, Pool-Zobel BL, De Méo MP, Collins A. The single cell gel electrophoresis assay (comet assay): A European review. Mutat. Res. [Internet]. 1993; 288(1):47–63. doi: https://doi.org/cwdg6z
Nandhakumar S, Parasuraman S, Shanmugam MM, Ramachandra, RK, Parkash C, Vishnu BB. Evaluation of DNA damage using single-cell gel electrophoresis (Comet Assay). J. Pharmacol. Pharmacother. [Internet]. 2011; 2(2):107–111. doi: https://doi.org/dmfjnf
McKenna DJ, McKeown SR, McKelvey-Martin VJ. Potential use of the comet assay in the clinical management of cancer. Mutagen. [Internet]. 2008; 23(3):183–190. doi: https://doi.org/dxn6ct
Kopjar N, Garaj-Vrhovac V, Milas I. Assessment of chemotherapy-induced DNA damage in peripheral blood leukocytes of cancer patients using the alkaline comet assay. Teratog. Carcinog. Mutagen. [Internet]. 2002; 22(1):13–30. doi: https://doi.org/ffh7xz
Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol. Biotechnol. [Internet]. 2004; 26: 249–261. doi: https://doi.org/b4xr3f
Reza-Khorramizadeh M, Saadat F. Animal models for human disease. In: Verma AS, Singh A, editors. Animal Biotechnology. 2nd. ed. [Internet]. Boston: Academic Press; 2020. p 153–171. doi: https://doi.org/mdkn
Mukherjee P, Roy S, Ghosh D, Nandi SK. Role of animal models in biomedical research: a review. Lab. Anim. Res. [Internet]. 2022; 38:18. doi: https://doi.org/mdkp
Robinson NB, Krieger K, Khan FM, Huffman W, Chang M, Naik A, Yongle R, Hameed I, Krieger K, Girardi LN, Gaudino M. The current state of animal models in research: A review. Int J Surg. [Internet]. 2019; 72:9-13. doi: https://doi.org/ghw9fn
Morgan SJ, Elangbam CS, Berens S, Janovitz E, Vitsky A, Zabka T, Conour L. Use of animal models of human disease for nonclinical safety assessment of novel pharmaceuticals. Toxicol. Pathol. [Internet]. 2013; 41(3):508–518. doi: https://doi.org/mdsf
Inglebert M, Dettwiler M, Hahn K, Letko A, Drogemuller C, Doench J, Brown A, Memari Y, Davies HR, Degasperi A, Nik-Zainal S, Rottenberg S. A living biobank of canine mammary tumor organoids as a comparative model for human breast cancer. Sci. Rep. [Internet]. 2022; 12:18051. doi: https://doi.org/gq486f
Abdelmegeed SM, Mohammed S. Canine mammary tumors as a model for human disease. Oncol. Lett. [Internet]. 2018; 15(6):8195–8205. doi: https://doi.org/mdsg
Gray M, Meehan J, Martínez-Pérez C, Kay C, Turnbull AK, Morrison LR, Pang LY, Argyle D. Naturally-Occurring Canine Mammary Tumors as a Translational Model for Human Breast Cancer. Front Oncol. [Internet]. 2020; 10:617. doi: https://doi.org/mdsh
Lutful-Kabir FM, Alvarez CE, Bird RC. Canine Mammary Carcinomas: A Comparative Analysis of Altered Gene Expression. Vet. Sci. China. [Internet]. 2015; 3(1):1. doi: https://doi.org/mdsj
Nguyen F, Peña L, Ibisch C, Loussouarn D, Gama A, Rieder N, Belousov A, Campone M, Abadie J. Canine invasive mammary carcinomas as models of human breast cancer. Part 1: natural history and prognostic factors. Breast Cancer Res. Treatm. [Internet]. 2018; 167:635–648. doi: https://doi.org/gc2pps
Abadie J, Nguyen F, Loussouarn D, Peña L, Gama A, Rieder N, Belousov A, Bemelmans I, Jaillardon L, Ibisch C, Campone M. Canine invasive mammary carcinomas as models of human breast cancer. Part 2: immunophenotypes and prognostic significance. Breast Cancer Res. Treatm. [Internet]. 2018; 167:459–468. doi: https://doi.org/gcxgxv
Nance RL, Sajib AM, Smith BF. Canine models of human cancer: Bridging the gap to improve precision medicine. Prog. Mol. Biol. Transl. Sci. [Internet]. 2022; 189(1):67–99. doi: https://doi.org/mdsk
Gardner HL, Fenger JM, London CA. Dogs as a Model for Cancer. Ann. Rev. Anim. Biosci. [Internet]. 2016; 4:199–222. doi: https://doi.org/gh6r4d
Lawrence J, Cameron D, Argyle D. Species differences in tumour responses to cancer chemotherapy. Philos Trans. R. Soc. Lond. B. Biol. Sci. [Internet]. 2015; 370(1673):20140233. doi: https://doi.org/mdsn
LeBlanc AK, Mazcko CN. Improving human cancer therapy through the evaluation of pet dogs. Nat. Rev. Cancer. [Internet]. 2020; 20:727–742. doi: https://doi.org/gpnwrm
Sokal RR, Rolf FJ. Biometry: The Principles and Practice of Statistics in Biological Research. J. R. Stat. Soc. Ser. A-G. [Internet]. 1970; 133(1):102 https://doi.org/dmx5x6
Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat. Meth. [Internet]. 2012; 9:671–675. doi: https://doi.org/gcwb4q
Gyori BM, Venkatachalam G, Thiagarajan PS, Hsu D, Clement MV. OpenComet: an automated tool for comet assay image analysis. Redox Biol. [Internet]. 2014; 2:457–465. doi: https://doi.org/gsn4qz
Tice RR, Agurell E, Anderson D, Burlinson B, Hartmann A, Kobayashi H, Miyamae Y, Rojas E, Ryu JC, Sasaki YF. Single cell gel/comet assay: guidelines for in vitro and in vivo genetic toxicology testing. Environ. Mol. Mutagen. [Internet]. 2000; 35(3):206–221. doi: https://doi.org/bbj2dg
Kumaravel TS, Vilhar B, Faux SP, Jha AN. Comet Assay measurements: a perspective. Cell Biol. Toxicol. [Internet]. 2009; 25:53–64. doi: https://doi.org/dm72kx
Miskinich-Lugo ME, Riveros-Duré CD, Quintana-Rotela AA, Ibáñez-Franco EJ, Cabañas-Cristaldo JD, Martínez-Ruiz-Díaz M, Britez DV, Medina-Méreles KG, Montiel DE. Efectos adversos relacionados a infusión endovenosa de ciclofosfamida en pacientes de un hospital de referencia. Rev. Parag. Reumatol. [Internet]. 2022; 8(1):11–15. doi: https://doi.org/mds3
Serrano Frago P, Allepuz-Losa C, Gil-Martínez P, Allué-López M, Mallén-Mateo E, Sancho-Serrano C, Rioja-Sanz. Tratamiento de la cistitis hemorrágica por ciclofosfamida. Revisión de la literatura a propósito de un caso. Actas Urol. Esp. [Internet]. 2005; 29(2):230–233. doi: https://doi.org/f2jf2q
Zubieta R, Retamal MG, Méndez G, Vela I, Facundo J, Manríquez L, López PJ, Letelier N, Escala JM. Cistitis crónica fibrótica-telangectásica por ciclofosfamida. Rev. Chil. Urol. [Internet]. 2004 [cited 16 Aug 2023]; 69(2):179–182. Available in: https://goo.su/hOblfPJ.
Madeddu C, Neri M, Sanna E, Oppi S, Macciò A. Experimental Drugs for Chemotherapy- and Cancer-Related Anemia. J. Exp. Pharmacol. [Internet]. 2021; 13:593–611. doi: https://doi.org/mds5
Natalucci V, Virgili E, Calcagnoli F, Valli G, Agostini D, Zeppa SD, Barbieri, E, Emili, R. Cancer Related Anemia: An Integrated Multitarget Approach and Lifestyle Interventions. Nutrients. [Internet]. 2021; 13(2):482. doi: https://doi.org/gmmqmq
Todorova I, Simeonova G, Simeonov R, Dinev D. Efficacy and toxicity of doxorubicin and cyclophosphamide chemotherapy in dogs with spontaneous mammary tumours. Trakia J. Sci. [Internet]. 2005 [cited 28 Aug 2023]; 3(5):51–58. Available in: https://goo.su/Ibonk.
Withrow SJ, Page R, Vail DM. Withrow and MacEwen’s Small Animal Clinical Oncology. [Internet]. 5th Ed. St. Louis, MO, USA: Elsevier Saunders; 2012. 768 p. doi: https://doi.org/mds6
Simsek C, Esin E, Yalcin S. Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience. J. Oncol. [Internet]. 2019; 2019:5483791. doi: https://doi.org/gjk6kt
Soriano-Lorenzo J, García JS, Lima-Pérez M. Quimioterapia metronómica en pacientes con cáncer de mama metastásico. An. Fac. Med. [Internet]. 2020; 81(1):80-86. doi: https://doi.org/mds9
Soriano-García JL, Lima-Pérez M, González-González J, Batista-Albuerne N, López-Soto MV, Rodríguez-Menéndez M, Loys-Fernández, JL, Montejo-Viamontes, N. Quimioterapia metronómica con ciclofosfamida y metotrexato en pacientes con cáncer de mama metastásico en progresión. Rev. Cubana Med. [Internet]. 2009 [cited 24 Aug 2023]; 48(2):1-14. Available in: https://goo.su/wgEfvg.
Hartmann A, Herkommer K, Glück M, Speit G. DNA-damaging effect of cyclophosphamide on human blood cells in vivo and in vitro studied with the single-cell gel test (comet assay). Environm. Molec. Mutagen. [Internet]. 1995; 25(3):180-187. doi: https://doi.org/fn77z9
Hartmann A, Speit G. Genotoxic effects of chemicals in the single cell gel (SCG) test with human blood cells in relation to the induction of sister-chromatid exchanges (SCE). Mutat. Res. [Internet]. 1995; 346(1):49–56. doi: https://doi.org/c8tdwz
Anderson D, Bishop JB, Garner RC, Ostrosky-Wegman P, Selby PB. Cyclophosphamide: review of its mutagenicity for an assessment of potential germ cell risks. Mutat. Res. [Internet]. 1995; 330(1-2):115–181. doi: https://doi.org/cnr42g
Andersson M, Agurell E, Vaghef H, Bolcsfoldi G, Hellman B. Extended-term cultures of human T-lymphocytes and the comet assay: a useful combination when testing for genotoxicity in vitro? Mutat. Res. [Internet]. 2003; 540(1):43–55. doi: https://doi.org/dnw5v6
Yusuf AT, Vian L, Sabatier R, Cano JP. In vitro detection of indirect-acting genotoxins in the comet assay using Hep G2 cells. Mutat. Res. [Internet]. 2000; 468(2):227–234. doi: https://doi.org/ck8gxc
Uhl M, Helma C, Knasmüller S. Evaluation of the single cell gel electrophoresis assay with human hepatoma (Hep G2) cells. Mutat. Res. [Internet]. 2000; 468(2):213–225. doi: https://doi.org/fmzpq4
Robbiano L, Carrozzino R, Bacigalupo M, Corbu C, Brambilla G. Correlation between induction of DNA fragmentation in urinary bladder cells from rats and humans and tissue-specific carcinogenic activity. Toxicol. [Internet]. 2002; 179(1-2):115–128. doi: https://doi.org/cx53td
Frenzilli G, Bosco E, Barale R. Validation of single cell gel assay in human leukocytes with 18 reference compounds. Mutat. Res. [Internet]. 2000; 468(2):93–108. doi: https://doi.org/fpcds3
Kopjar N, Milas I, Garaj-Vrhovac V, Gamulin M. Alkaline comet assay study with breast cancer patients: evaluation of baseline and chemotherapy-induced DNA damage in non-target cells. Clin. Exp. Med. [Internet]. 2006; 6:177–190. doi: https://doi.org/fxbrnm
Paz MFCJ, de Alencar MVOB, Gomes Junior AL, da Conceição-Machado K, Islam MT, Ali ES, Shill MC, Ahmed MI, Uddin SJ, da Mata AMOF, de Carvalho RM, da Conceição-Machado K, Sobral ALP, da Silva FCC, de Castro e Souza JM, Arcanjo DDR, Ferreira PMP, Mishra SK, da Silva J, de Carvalho Melo-Cavalcante AA. Correlations between Risk Factors for Breast Cancer and Genetic Instability in Cancer Patients-A Clin. Perspect. Study. Front. Genet. [Internet]. 2017; 8:236. doi: https://doi.org/gc4stv
Smith TR, Miller MS, Lohman KK, Case LD, Hu JJ. DNA damage and breast cancer risk. Carcinogen. [Internet]. 2003; 24(5):883–889. doi: https://doi.org/d3f5m9
Lam FC. The DNA damage response - from cell biology to human disease. J. Transl. Genet. Genom. [Internet]. 2022; 6:204–222. doi: https://doi.org/mdth
Torgovnick A, Schumacher B. DNA repair mechanisms in cancer development and therapy. Front. Genet. [Internet]. 2015; 6:157. doi: https://doi.org/gnsfph
Chatterjee N, Walker GC. Mechanisms of DNA damage, repair, and mutagenesis. Environ. Mol. Mutagen. [Internet]. 2017; 58(5):235–263. doi: https://doi.org/f99rs5
Derechos de autor 2024 Lorena Elizabeth Chalco–Torres, José Atilio Aranguren–Méndez, Ana Elizabeth Guerrero–López, Mauro Nirchio–Tursellino
Esta obra está bajo licencia internacional Creative Commons Reconocimiento-NoComercial-CompartirIgual 4.0.
