Обнаружение заболеваний по анализу летучих органических соединений: I. Собаки-детекторы


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Аннотация

В работе представлен обзор современных исследований роли летучих органических соединений в диагностике онкологических заболеваний. Рассмотрены возможности обоняния собак, использование животных-биосенсоров в выделении больных организмов среди здоровых, сложности этого метода, сравнение его с инструментальными методами исследований. В обзор включены результаты собственных исследований авторов и литературные данные об особенностях применения обученных животных в изучении летучих органических соединений, связанных с развитием онкологических заболеваний. Предложены возможные пути развития этой области исследований.

Об авторах

Е. И. Родионова

Федеральное государственное бюджетное учреждение науки Институт проблем передачи информации им. А.А. Харкевича РАН

Email: a.rodionova@gmail.com
127051, Москва, Большой Каретный пер., д. 19, стр. 1

О. О. Кирюхина

Федеральное государственное бюджетное учреждение науки Институт проблем передачи информации им. А.А. Харкевича РАН

127051, Москва, Большой Каретный пер., д. 19, стр. 1

А. В. Пенто

Институт общей физики им. А.М. Прохорова РАН

119991 ГСП-1, Москва, ул. Вавилова, д. 38

С. М. Никифоров

Институт общей физики им. А.М. Прохорова РАН

119991 ГСП-1, Москва, ул. Вавилова, д. 38

Список литературы

  1. Amundsen T., Sundstrøm S., Buvik T., Gederaas O.A., Haarverstad R. Can dogs smell lung cancer? First study using exhaled breath and urine screening in unselected patients with suspected lung cancer. Acta Oncol. 2014. V. 53 P. 307–315. https://doi.org/10.3109/0284186X.2013.819996
  2. Arakawa H., Arakawa K., Deak T. Acute illness induces the release of aversive odor cues from adult, but not prepubertal, male rats and suppresses social investigation by conspecifics. Behav. Neurosci. 2009. V. 123. P. 964–978. https://doi.org/10.1037/a0017114
  3. Arakawa H., Cruz S., Deak T. From models to mechanisms: odorant communication as a key determinant of social behavior in rodents during illness-associated states. Neurosci Biobehav Rev. 2011. V. 35(9). P. 1916–1928. https://doi.org/10.1016/j.neubiorev.2011.03.007
  4. Bijland L.R., Bomers M.K., Smulders Y.M. Smelling the diagnosis: a review on the use of scent in diagnosing disease. Neth. J. Med. 2013. V. 71. P. 300–307.
  5. Buszewski B., Ligor T., Jezierski T., Wenda-Piesik A., Walczak M., Rudnicka J. Identification of volatile lung cancer markers by gas chromatography mass spectrometry: comparison with discrimination by canines. Anal. Bioanal. Chem. 2012. V. 404(1). P. 141–146
  6. Concha A., Mills D.S., Feugier A., Zulch H., Guest C., Harris R., Pike T.W. Using sniffing behavior to differentiate true negative from false negative responses in trained scent-detection dogs. Chem. Senses. 2014. V. 39. P. 749–754. https://doi.org/10.1093/chemse/bju045
  7. Concha A.R., Guest C.M., Harris R., Pike T.W., Feugier A., Zulch H., Mills D.S. Canine olfactory thresholds to amyl acetate in a biomedical detection scenario. Front. Vet. Sci. 2019. V. 5. P. 345. https://doi.org/10.3389/fvets.2018.00345
  8. Concha A. Detection of human diseases for medical diagnostics. In: Lazarowski, L. (eds) Olfactory Research in Dogs. 2023. Springer, Cham. P. 291-331. https://doi.org/10.1007/978-3-031-39370-9_12
  9. Cornu J.N., Cancel-Tassin G., Ondet V., Girardet C., Cussenot O. Olfactory detection of prostate cancer by dogs sniffing urine: a step forward in early diagnosis. Eur. Urol. 2011. V. 59. P. 197–201. https://doi.org/10.1016/j.eururo.2010.10.006
  10. Crawford M.A., Chang C.L., Browne C.M., Hopping S., Jameson M.B., Edwards T.L. Breath versus saliva for lung cancer detection with dogs. ERJ Open Res. 2025. https://doi.org/10.1183/23120541.00914-2024
  11. Elliker K.R., Sommerville B.A., Broom D.M., Neal D.E., Armstrong S., Williams H.C. Key considerations for the experimental training and evaluation of cancer odour detection dogs: lessons learnt from a double-blind, controlled trial of prostate cancer detection. BMC Urol. 2014. V. 14. P. 1-9. https://doi.org/10.1186/1471-2490-14-22
  12. Ferkin M.H. Odor communication and mate choice in rodents. Biology. 2018. V. 7(1). P. 13. https://doi.org/10.3390/biology7010013
  13. Fischer-Tenhagen C., Johnen D., Nehls I., Becker R. A proof of concept: are detection dogs a useful tool to verify potential biomarkers for lung cancer? Front. Vet. Sci. 2018. V. 5. P. 1–6. https://doi.org/10.3389/fvets.2018.00052
  14. Ghirlanda S.; Enquist M. A century of generalization. Anim. Behav. 2003. V. 66. P. 15–36. https://doi.org/10.1006/anbe.2003.2174
  15. Giró Benet J., Seo M., Khine M., Gumà Padró J., Pardo Martnez A., Kurdahi F. Breast cancer detection by analyzing the volatile organic compound (VOC) signature in human urine. Sci. Rep. 2022. V. 12. P. 14873. https://doi.org/10.1038/s41598– 022-17795-8
  16. Gordon R.T., Schatz C.B., Myers L.J., Kosty M., Gonczy C., Kroener J., Tran M., Kurtzhals P., Heath S., Koziol J.A., Arthur N. The use of canines in the detection of human cancers. J. Altern. Complement. Med. 2008. V. 14. P. 61–67. https://doi.org/10.1089/acm.2006.6408
  17. Guerrero-Flores H., Apresa-García T., Garay-Villar Ó., Sánchez-Pérez A., Flores-Villegas D., Bandera-Calderón A., Garcia-Palacios R., Rojas-Sanchez T., Romero-Morelos P., Sanchez-Albor V., Mata O. A non-invasive tool for detecting cervical cancer odor by trained scent dogs. BMC Cancer. 2017. V. 17. P. 1–8. https://doi.org/10.1186/s12885-016-2996-4
  18. Guest C., Harris R., Sfanos K.S., Shrestha E., Partin A.W., Trock B., Mangold L., Bader R., Kozak A., Mclean S., Simons J. Feasibility of integrating canine olfaction with chemical and microbial profiling of urine to detect lethal prostate cancer. PLoS One. 2021 V. 16(2). P. e0245530. https://doi.org/10.1371/journal.pone.0245530
  19. Guest C.M., Harris R., Anjum I., Concha A.R., Rooney N.J. A lesson in standardization–Subtle aspects of the processing of samples can greatly affect dogs’ learning. Front. Vet. Sci. 2020. V. 7. P. 525 [online]. https://doi.org/10.3389/fvets.2020.00525
  20. Hakim M., Broza Y.Y., Barash O., Peled N., Phillips M., Amann A., Haick H. Volatile organic compounds of lung cancer and possible biochemical pathways. Chem. Rev. 2012. V. 112. P. 5949–5966. https://doi.org/10.1021/cr300174a
  21. Hardin D.S., Anderson W., Cattet J. Dogs can be successfully trained to alert to hypoglycemia samples from patients with type 1 diabetes. Diabetes Therapy. 2015. V. 6(4). P. 509-517. https://doi.org/10.1007/s13300-015-0135-x
  22. Hermieu J.F., Hermieu M., Roux A., Desquilbet L., Hermieu N., Gallet C., Xylinas E., De La Taille A., Grandjean D. Contribution of canine olfaction in the diagnostic strategy of intermediate and high-risk prostate cancer: a double-blind validation study. World. J. Urol. 2024. V. 42. P. 497. https://doi.org/10.1007/s00345-024-05201-z
  23. Holt L., Johnston S.V. From small to tall: breed-varied household pet dogs can be trained to detect Parkinson’s Disease. Animal Cognition. 2024. V. 27(1). P. 62. https://doi.org/10.1007/s10071-024-01902-5
  24. Hori S.S., Gambhir S.S. Mathematical model identifies blood biomarker-based early cancer detection strategies and limitations. Sci Transl Med. 2011. V. 3(109). P. 109–116. https://doi: 10.1126/scitranslmed.3003110
  25. Horvath G., Järverud G.A.K., Järverud S., Horváth I. Human ovarian carcinomas detected by specific odor. Integr. Cancer. Ther. 2008. V. 7. P. 76–80. https://doi.org/10.1177/1534735408319058
  26. Horvath G., Andersson H., Paulsson G. Characteristic odour in the blood reveals ovarian carcinoma. BMC Cancer. 2010. V. 10. P. 643 https://doi.org/10.1186/1471-2407-10-643
  27. Horvath G., Andersson H., Nemes S. Cancer odor in the blood of ovarian cancer patients: a retrospective study of detection by dogs during treatment, 3 and 6 months afterward. BMC Cancer. 2013. V. 13. P. 1-7. https://doi.org/10.1186/1471-2407-13-396
  28. Jendrny P., Twele F., Meller S., Schulz C., von Köckritz-Blickwede M., Osterhaus A.D., Ebbers H., Ebbers J., Pilchová V., Pink I., Welte T. Scent dog identification of SARS-CoV-2 infections in different body fluids. BMC Infect. Dis. 2021. P. 1-4. https://doi.org/10.1186/s12879-021-06411-1
  29. Jezierski T., Walczak M., Ligor T., Rudnicka J., Buszewski B. Study of the art: canine olfaction used for cancer detection on the basis of breath odour. Perspectives and limitations. J Breath Res. 2015. V. 9. P. 027001. http://iopscience.iop.org/1752-7163/9/2/027001
  30. Junqueira H., Quinn T.A., Biringer R., Hussein M., Smeriglio C., Barrueto L., Finizio J., Huang X.Y. Accuracy of canine scent detection of non–small cell lung cancer in blood serum. J. Am. Osteopathic Assoc. 2019. V. 119(7). P. 413–418. https://doi.org/10.7556/jaoa.2019.077
  31. Kane S.A., Lee Y.E., Essler J.L., Mallikarjun A., Preti G., Verta A., DeAngelo A., Otto C.M. Canine discrimination of ovarian cancer through volatile organic compounds. Talanta. 2022. V. 250. P. 123729. https://doi.org/10.1016/j.talanta.2022.123729
  32. Kavaliers M., Choleris E., Pfaff D.W. Recognition and avoidance of the odors of parasitized conspecifics and predators: differential genomic correlates. Neurosci. Biobehav. Rev. 2005. V. 29. P. 1347– 1359. https://doi.org/10.1016/j.neubiorev.2005.04.011
  33. Kiesecker J.M., Skelly D.K., Beard K.H., Preisser E. Behavioral reduction of infection risk. Proc. Natl. Acad. Sci. USA. 1999. V. 96. P. 9165–9168. https://doi.org/10.1073/pnas.96.16.9165
  34. Kimball B.A., Opiekun M., Yamazaki K., Beauchamp G.K. Immunization alters body odor. Physiol. Behav. 2014. V. 128. P. 80-85. https://doi.org/10.1016/j.physbeh.2014.01.022
  35. Kimball B.A., Yamazaki K., Kohler D., Bowen R.A., Muth J.P., Opiekun M., Beauchamp G.K. Avian influenza infection alters fecal odor in mallards. PLoS One. 2013 V. 8(10). P. e75411. https://doi.org/10.1371/journal.pone.0075411
  36. Kochevalina M.Y., Bukharina A.B., Trunov V.G., Pento A.V., Morozova O.V., Kogun’ G.A., Simanovsky Y.O., Nikiforov S.M., Rodionova E.I. Changes in the urine volatile metabolome throughout growth of transplanted hepatocarcinoma. Sci. Rep. 2022. V. 12(1). P. 7774. https://doi.org/10.1038/s41598-022-11818-0
  37. Kure S., Iida S., Yamada M., Takei H., Yamashita N., Sato Y., Miyashita M. Breast cancer detection from a urine sample by dog sniffing. Research Square. 2020. https://doi.org/10.21203/rs.3.rs-89484/v1
  38. Kure S., Iida S., Yamada M., Takei H., Yamashita N., Sato Y., Miyashita M. Breast cancer detection from a urine sample by dog sniffing: a preliminary study for the development of a new screening device, and a literature review. Biology. 2021. V.10(6). P. 517. https://doi.org/10.3390/biology10060517
  39. Lima A.R., Pinto J., Azevedo A.I., Barros-Silva D., Jerónimo C., Henrique R., de Lourdes Bastos M., Guedes de Pinho P., Carvalho M. Identification of a biomarker panel for improvement of prostate cancer diagnosis by volatile metabolic profiling of urine. Br. J. Cancer. 2019. V. 121(10). P. 857–868. https://doi.org/10.1038/s41416-019-0585-4
  40. Lippi G., Cervellin G. Canine olfactory detection of cancer versus laboratory testing: myth or opportunity? Clin. Chem. Lab. Med. 2012. V. 50. P. 435–439. doi.org/10.1515/cclm.2011.672
  41. Lippi G., Heaney L.M. The “olfactory fingerprint”: can diagnostics be improved by combining canine and digital noses? Clin. Chem. Lab. Med. 2020. V. 58. P. 958–967. https://doi.org/10.1515/cclm2019-1269
  42. Maa E., Arnold J., Ninedorf K., Olsen H. Canine detection of volatile organic compounds unique to human epileptic seizure. Epilepsy Behav. 2021. V. 115. P. 107690. https://doi.org/10.1016/j.yebeh.2020.107690
  43. Matsumura K., Opiekun M., Oka H., Vachani A., Albelda S.M., Yamazaki K., Beauchamp G.K. Urinary volatile compounds as biomarkers for lung cancer: a proof of principle study using odor signatures in mouse models of lung cancer. PLoS One. 2010. V. 5. P. e8819. https://doi.org/10.1371/journal.pone.0008819
  44. McCulloch M., Jezierski T., Broffman M., Hubbard A, Turner K., Janecki T. Diagnostic accuracy of canine scent detection in early– and late-stage lung and breast cancers. Integr. Cancer Ther. 2006. V. 5(1). P. 30-39. https://doi.org/10.1177/153473540528509
  45. Moser E., McCulloch M. Canine scent detection of human cancers: a review of methods and accuracy. J. Vet. Behav. 2010. V. 5(3). P. 145–152. https://doi.org/10.1016/j.jveb.2010.01.002
  46. Moser E, Ariella Y., Bizo L., Brown W.Y. Olfactory Generalization in Detector Dogs” Animals. 2019. V. 9. P. 702. https://doi.org/10.3390/ani9090702
  47. Ortal A., Rodríguez A., Solis-Hernández M.P. Proof of concept for the use of trained sniffer dogs to detect osteosarcoma. Sci. Rep. 2022. V. 12. P. 6911 https://doi.org/10.1038/s41598-022-11013-1
  48. Pashkovski S.L., Iurilli G., Brann D., Chicharro D., Drummey K., Franks K., Panzeri S., Datta S.R. Structure and flexibility in cortical representations of odour space. Nature. 2020. V. 583(7815). P. 253–258. https://doi.org/10.1038/s41586-020-2451-1
  49. Picket D.P., Manucy G.P., Walker D.B., Hall S.B., Walker J.C. Evidence of canine olfactory detection of melanoma. Appl. Animal. Behav. Sci. 2004. V. 89(1–2). P. 107–116. https://doi.org/10.1016/j.applanim.2004.04.008
  50. Pirrone F., Albertini M. Olfactory detection of cancer by trained sniffer dogs: a systematic review of the literature. J. Vet. Behav. 2017. V. 19. P. 105–118. https://doi.org/10.1016/j.jveb.2017.03.004
  51. Riedlova P., Tavandzis S., Kana J., Tobiasova M. Olfactometric diagnosis of lung cancer by canine scent—a double-blinded study. Complement. Ther. Med. 2022. V. 64. P. 102800. https://doi.org/10. 1016/j.ctim.2022.102800
  52. Rodionova E., Morozova O., Kochevalina M., Kogun G., Trunov V.G. Physical Trauma Alters the Spectrum of Volatile Organic Compounds. Biol. Bull. 2025. (In press.)
  53. Rodionova E.I., Kochevalina M.Y., Kotenkova E.V., Morozova O.V., Kogun’ G.A., Bataeva E.L., Ambaryan A.V. Detection of volatile organic compounds associated with hepatocellular carcinoma by macrosmatic animals: Approaches to the search for new tumor markers. Biol. Bull. 2015. V. 42. P. 239-245. https://doi.org/10.1134/S1062359015030103
  54. Rudnicka J., Walczak M., Kowalkowski T., Jezierski T., Buszewski B. Determination of volatile organic compounds as potential markers of lung cancer by gas chromatography–mass spectrometry versus trained dogs. Sens. Actuat. B: Chem. 2014. V. 202. P. 615–621. https://doi.org/10.1016/j.snb.2014.06.006
  55. Schoon A., De Jonge D., Hilverink P. How dogs learn to detect colon cancer—optimizing the use of training aids. J. Vet. Behav. 2020. V. 35. P. 38–44. https://doi.org/10.1016/j.jveb.2019.10.006
  56. Shirasu M., Touhara K. The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem. 2011. V. 150(3). P. 257–266. https://doi.org/10.1093/jb/mvr090
  57. Sonoda H., Kohnoe S., Yamazato T., Satoh Y., Morizono G., Shikata K., Morita M., Watanabe A., Morita M., Kakeji Y., Inoue F. Colorectal cancer screening with odour material by canine scent detection. Gut. 2011. V. 60. P. 814–819. https://doi.org/10.1136/gut.2010.218305
  58. Taverna G., Tidu L., Grizzi F., Torri V., Mandressi A., Sardella P., La Torre G., Cocciolone G., Seveso M., Giusti G., Hurle R. Olfactory system of highly trained dogs detects prostate cancer in urine samples. J. Urol. 2015. V. 193. P. 1382–1387. https://doi.org/10.1016/j.juro.2014.09.099
  59. Urbanova L., Vylmankova V., Krisova S., Pacik D., Necas A. Intensive training technique utilizing the dog’s olfactory abilities to diagnose prostate cancer in men. Acta Vet. Brno. 2015.V. 84. P. 77–82. https://doi.org/10.2754/avb201585010077
  60. Walker D.B., Walker J.C., Cavnar P. J., Taylor J. L., Pickel D. H., Hall S. B., Suarez J.C. Naturalistic quantification of canine olfactory sensitivity. Appl. Anim. Behav. Sci. 2006. V. 97(2-4). P. 241-254. https://doi.org/10.1016/j.applanim.2005.07.009
  61. Walczak M. Operant conditioning of dogs for detection of odour markers of cancer diseases. PhD thesis. Institute of Genetics and Animal Breeding of Polish Academy of Sciences. 2009. (in Polish)
  62. Walczak M., Jezierski T., Górecka-Bruzda A., Sobczyńska M., Ensminger J. Impact of individual training parameters and manner of taking breath odor samples on the reliability of canines as cancer screeners. J. Vet. Behav. Clin. Appl. Res. 2012. V. 7(5). P. 283-294. https://doi.org/10.1016/j.jveb.2012.01.001
  63. Willis C.M., Britton L.E., Harris R., Wallace J., Guest C.M. Volatile organic compounds as biomarkers of bladder cancer: sensitivity and specificity using trained sniffer dogs. Cancer Biomark. 2010. V. 8. P. 145–153. https://doi.org/10.3233/cbm-2011-0208
  64. Willis C.M., Church S.M., Guest C.M., Cook W.A., McCarthy N., Bransbury A.J., Church M.R., Church J.C. Olfactory detection of human bladder cancer by dogs: proof of principle study. BMJ. 2004. V. 329(7468). P. 712.https://doi.org/10.1136/bmj.329.7468.712
  65. Yamamoto A., Kamoi S., Kurose K., Ito M., Takeshita T., Kure S., Sakamoto K., Sato Y., Miyashita M. The trained sniffer dog could accurately detect the urine samples from the patients with cervical cancer, and even cervical intraepithelial neoplasia grade 3: a pilot study. Cancers. 2020. V. 12(11). P. 3291. https://doi.org/10.3390/cancers1211329

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