Тромбогеморрагические осложнения при лечении больных острым лимфобластным лейкозом L-аспарагиназой

Г.М. Галстян, О.А. Полеводова, А.В. Баженов, В.В. Троицкая, О.А. Гаврилина, Д.Г. Гительзон, А.Э. Васильев, Е.Н. Паровичникова

ФГБУ «НМИЦ гематологии» Минздрава России, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167

Для переписки: Геннадий Мартинович Галстян, д-р мед. наук, Новый Зыковский пр-д, д. 4, Москва, Российская Федерация, 125167; тел.: +7(916)488-50-73; e-mail: gengalst@gmail.com

Для цитирования: Галстян Г.М., Полеводова О.А., Баженов А.В. и др. Тромбогеморрагические осложнения при лечении больных острым лимфобластным лейкозом L-аспарагиназой. Клиническая онкогематология. 2018;11(1):89-99.

DOI: 10.21320/2500-2139-2018-11-1-89-99


РЕФЕРАТ

Настоящая статья представляет собой обзор литературы, посвященный применению L-аспарагиназы (АСП) при остром лимфобластном лейкозе (ОЛЛ), с описанием 2 собственных клинических наблюдений. Лечение АСП при проведении индукции ремиссии осложнилось у пациентов венозными тромбозами и кровоизлиянием в ЦНС. В обоих случаях эти осложнения возникли на фоне сниженной плазменной активности антитромбина III (АТ), гипофибриногенемии и тромбоцитопении. Обсуждаются факторы риска возникновения тромбогеморрагических осложнений у больных ОЛЛ во время лечения АСП, роль в их развитии сочетанной терапии АСП с антрациклинами, пероральными контрацептивами, глюкокортикостероидами, наличия тромбофилии и центрального венозного катетера. Описаны возможные механизмы развития тромбозов, определены наиболее вероятные сроки их возникновения, локализация. В статье приводятся различные варианты профилактики и лечения тромбогеморрагических осложнений у больных ОЛЛ во время лечения АСП. Рекомендуется у всех больных ОЛЛ, получающих АСП, исследовать в плазме концентрацию фибриногена и активность АТ до начала лечения, на 3-й день после введения препарата и далее каждые 5–7 дней на протяжении 3 нед. после введения. Новые пероральные антикоагулянты не зависят от активности АТ в крови и могут использоваться для профилактики и лечения тромботических осложнений, связанных с АСП. Приводятся рекомендации по коррекции содержания АТ и гипофибриногенемии.

Ключевые слова: L-аспарагиназа, осложнения, тромбоз, тромбоэластография, антитромбин III, гипофибриногенемия, тромбоцитопения, новые пероральные антикоагулянты.

Получено: 16 августа 2017 г.

Принято в печать: 27 октября 2017 г.

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ЛИТЕРАТУРА

  1. Савченко В.Г., Паровичникова Е.Н., Афанасьев Б.В. и др. Национальные клинические рекомендации по диагностике и лечению острых миелоидных лейкозов взрослых. Гематология и трансфузиология. 2014;59(1):1–32. [Savchenko VG, Parovichnikova EN, Afanas’ev BV, et al. National clinical recommendations for the diagnosis and treatment of acute myeloid leukemia in adults. Gematologiya i transfuziologiya. 2014;59(1):1–32. (In Russ)]
  2. Asselin BL. The three asparaginases. In: Kaspers GJL, Pieters R, Veerman AJP, eds. Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol. 457. Boston: Springer; 1999. pp. 621–9. doi: 10.1007/978-1-4615-4811-9_69.
  3. Попа А.В. Возможности адекватного выбора различных препаратов аспарагиназы. Онкогематология. 2007;1:52–6. [Popa AV. The abilities of adequate choice of different asparaginase products. Onkogematologiya. 2007;1:52–6. (In Russ)]
  4. Priest JR, Ramsay NK, Steinherz PG, et al. A syndrome of thrombosis and hemorrhage complicating L-asparaginase therapy for childhood acute lymphoblastic leukemia. J Pediatr. 1982;100(6):984–9. doi: 10.1016/s0022-3476(82)80535-0.
  5. Caruso V, Iacoviello L, Castelnuovo A Di, et al. Thrombotic complications in childhood acute lymphoblastic leukemia : a meta-analysis of 17 prospective studies comprising 1752 pediatric patients. Blood. 2006;108(7):2216–22. doi: 10.1182/blood-2006-04-015511.
  6. Rozen L, Noubouossie D, Dedeken L, et al. Different profile of thrombin generation in children with acute lymphoblastic leukaemia treated with native or pegylated asparaginase: A cohort study. Pediatr Blood Cancer. 2017;26(2):294–301. doi: 10.1002/pbc.26228.
  7. Caruso V, Iacoviello L, Di Castelnuovo A, et al. Venous thrombotic complications in adults undergoing induction treatment for acute lymphoblastic leukemia: results from a meta-analysis. J Thromb Haemost. 2007;5(3):621–3. doi: 10.1111/j.1538-7836.2007.02383.x.
  8. Ranta S, Heyman MM, Jahnukainen K, et al. Antithrombin deficiency after prolonged asparaginase treatment in children with acute lymphoblastic leukemia. Blood Coagul Fibrinol.  2013;24(7):749–56. doi: 10.1097/mbc.0b013e328363b147.
  9. Abbott LS, Deevska M, Fernandez CV, et al. The impact of prophylactic fresh-frozen plasma and cryoprecipitate on the incidence of central nervous system thrombosis and hemorrhage in children with acute lymphoblastic leukemia receiving asparaginase. Blood. 2009;114(25):5146–51. doi: 10.1182/blood-2009-07-231084.
  10. Grace RF, Dahlberg SE, Neuberg D, et al. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols. Br J Haematol. 2011;152(4):452–9. doi: 10.1111/j.1365-2141.2010.08524.x.
  11. Merlen C, Bonnefoy A, Wagner E, et al. L-Asparaginase Lowers Plasma Antithrombin and Mannan-Binding-Lectin Levels: Impact on Thrombotic and Infectious Events in Children With Acute Lymphoblastic Leukemia. Pediatr Blood Cancer. 2015;62(8):1381–7. doi: 10.1002/pbc.25515.
  12. Mizrahi T, Leclerc J-M, David M, et al. ABO Group as a Thrombotic Risk Factor in Children With Acute Lymphoblastic Leukemia: A Retrospective Study of 523 Patients. J Pediatr Hematol Oncol. 2015;37(5):e328–32. doi: 10.1097/mph.0000000000000333.
  13. Lauw MN, Van der Holt B, Middeldorp S, et al. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation. Thromb Haemost. 2013;109(4):633–42. doi: 10.1160/th12-11-0845.
  14. Mitchell LG, Andrew M, Hanna K, et al. A prospective cohort study determining the prevalence of thrombotic events in children with acute lymphoblastic leukemia and a central venous line who are treated with L-asparaginase: results of the Prophylactic Antithrombin Replacement in Kids with Acute Lymphoblastic Leukemia Treated with Asparaginase (PARKAA) Study. Cancer. 2003;97(2):508–16. doi: 10.1002/cncr.11042.
  15. Sibai H, Seki JT, Wang TQ, et al. Venous thromboembolism prevention during asparaginase-based therapy for acute lymphoblastic leukemia. Curr Oncol. 2016;23(4):e355–61. doi: 10.3747/co.23.3077.
  16. Goyal G, Bhatt VR. L-asparaginase and venous thromboembolism in acute lymphocytic leukemia. Fut Oncol. 2015;11(17):2459–70. doi: 10.2217/fon.15.114.
  17. Couturier M-A, Huguet F, Chevallier P, et al. Cerebral venous thrombosis in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma during induction chemotherapy with l-asparaginase: The GRAALL experience. Am J Hematol. 2015;90(11):986–91. doi: 10.1002/ajh.24130.
  18. Wani NA, Kosar T, Pala NA, Qureshi UA. Sagittal sinus thrombosis due to L-asparaginase. J Pediatr Neurosci. 2010;5(1):32–5. doi: 10.4103/1817-1745.66683.
  19. Guzman-Uribe P, Vargas-Ruiz AG. Thrombosis in Leukemia: Incidence, Causes, and Practical Management. Curr Oncol Rep. 2015;17(5):444. doi: 10.1007/s11912-015-0444-2.
  20. Huguet F, Leguay T, Raffoux E, et al. Pediatric-inspired therapy in adults with philadelphia chromosome-negative acute lymphoblastic leukemia: The GRAALL-2003 study. J Clin Oncol. 2009;27(6):911–8. doi: 10.1200/jco.2008.18.6916.
  21. Santoro N, Colombini A, Silvestri D, et al. Screening for coagulopathy and identification of children with acute lymphoblastic leukemia at a higher risk of symptomatic venous thrombosis: an AIEOP experience. J Pediatr Hematol Oncol. 2013;35(5):348–55. doi: 10.1097/mph.0b013e31828dc614.
  22. Pui C, Chesney CM, Bergum PW, et al. Lack of pathogenetic role of proteins C and S in thrombosis associated with asparaginase-prednisone-vincristine therapy for leukaemia. Br J Haematol. 1986;64(2):283–90. doi: 10.1111/j.1365-2141.1986.tb04121.x.
  23. Mauz-Korholz C, Junker R, Gobel U, Nowak-Gottl U. Prothrombotic risk factors in children with acute lymphoblastic leukemia treated with delayed E. coli asparaginase (COALL-92 and 97 protocols). Thromb Haemost. 2000;83(6):840–3.
  24. Risseeuw-Appel IM, Dekker I, Hop WC, Hahlen K. Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: a randomized study. Med Pediatr Oncol. 1994;23(4):335–43. doi: 10.1002/mpo.2950230404.
  25. Domenech C, Thomas X, Chabaud S, et al. L-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: Results of the GRASPALL 2005-01 randomized trial. Br J Haematol. 2011;153(1):58–65. doi: 10.1111/j.1365-2141.2011.08588.x.
  26. Nowak-Gottl U, Ahlke E, Fleischhack G, et al. Thromboembolic events in children with acute lymphoblastic leukemia (BFM protocols): prednisone versus dexamethasone administration. Blood. 2003;101(7):2529–33. doi: 10.1182/blood-2002-06-1901.
  27. Hernandez-Espinosa D, Minano A, Ordonez A, et al. Dexamethasone induces a heat-stress response that ameliorates the conformational consequences on antithrombin of L-asparaginase treatment. J Thromb Haemostasis. 2009;7(7):1128–33. doi: 10.1111/j.1538-7836.2009.03449.x.
  28. Hunault-Berger M, Chevallier P, Delain M, et al. Changes in antithrombin and fibrinogen levels during induction chemotherapy with L-asparaginase in adult patients with acute lymphoblastic leukemia or lymphoblastic lymphoma. Use of supportive coagulation therapy and clinical outcome: The CAPELAL study. Haematologica. 2008;93(10):1488–94. doi: 10.3324/haematol.12948.
  29. Ueno T, Ohtawa K, Mitsui K, et al. Cell cycle arrest and apoptosis of leukemia cells induced by L-asparaginase. Leukemia. 1997;11(11):1858–61. doi: 10.1038/sj.leu.2400834.
  30. Sugimoto K, Suzuki HI, Fujimura T, et al. A clinically attainable dose of L-asparaginase targets glutamine addiction in lymphoid cell lines. Cancer Sci. 2015;106(11):1534–43. doi: 10.1111/cas.12807.
  31. De Stefano V, Za T, Ciminello A, et al. Haemostatic alterations induced by treatment with asparaginases and clinical consequences. Thromb Haemost. 2015;113(2):247–61. doi: 10.1160/th14-04-0372.
  32. Giordano P, Molinari AC, Del Vecchio GC, et al. Prospective study of hemostatic alterations in children with acute lymphoblastic leukemia. Am J Hematol. 2010;85(5):325–30. doi: 10.1002/ajh.21665.
  33. Nowak-Gottl U, Boos J, Wolff J, et al. Asparaginase decreases clotting factors in vitro: a possible pitfall? Int J Clin Lab Res. 1995;25(3):146–8. doi: 10.1007/bf02592556.
  34. Bushman JE, Palmieri D, Whinna HC, Church FC. Insight into the mechanism of asparaginase-induced depletion of antithrombin III in treatment of childhood acute lymphoblastic leukemia. Leuk Res. 2000;24(7):559–65. doi: 10.1016/s0145-2126(00)00017-5.
  35. Priest JR, Ramsay NKC, Bennett AJ, et al. The effect of L-asparaginase on antithrombin, plasminogen, and plasma coagulation during therapy for acute lymphoblastic leukemia. J Pediatr. 1982;100(6):990–5. doi: 10.1016/s0022-3476(82)80536-2.
  36. Mazzucconi MG, Gugliotta L, Leone G, et al. Antithrombin III infusion suppresses the hypercoagulable state in adult acute lymphoblastic leukaemia patients treated with a low dose of Escherichia coli L-asparaginase. A GIMEMA study. Blood Coagul Fibrinol. 1994;5(1):23–8. doi: 10.1097/00001721-199402000-00004.
  37. Mitchell L, Andrew M, Hanna K, et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost. 2003;90(2):235–44. doi: 10.1160/th02-11-0283.
  38. Farrell K, Fyfe A, Allan J, et al. An antithrombin replacement strategy during asparaginase therapy for acute lymphoblastic leukemia is associated with a reduction in thrombotic events. Leuk Lymphoma. 2016;57(11):2567–74. doi: 10.3109/10428194.2016.1165815.
  39. Elhasid R, Lanir N, Sharon R, et al. Prophylactic therapy with enoxaparin during L-asparaginase treatment in children with acute lymphoblastic leukemia. Blood Coagul Fibrinol. 2001;12(5):367–70. doi: 10.1097/00001721-200107000-00005.
  40. Meister B, Kropshofer G, Klein-Franke A, et al. Comparison of low-molecular-weight heparin and antithrombin versus antithrombin alone for the prevention of symptomatic venous thromboembolism in children with acute lymphoblastic leukemia. Pediatr Blood Cancer. 2008;50(2):298–303. doi: 10.1002/pbc.21222.
  41. Plander M, Szendrei T, Bodo I, Ivanyi JL. Successful treatment with rivaroxaban of an extended superficial vein thrombosis in a patient with acquired antithrombin deficiency due to Peg-asparaginase treatment. Ann Hematol. 2015;94(7):1257–8. doi: 10.1007/s00277-015-2368-1.

Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения

В.С. Покровский, Е.М. Трещалина

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация


РЕФЕРАТ

Последние годы в области разработки новых противоопухолевых препаратов на основе ферментов продемонстрированы существенные достижения. Помимо L-аспарагиназы, которая применяется в онкогематологии уже более 30 лет, два фермента — L-аргининдезиминаза и ранпирназа — прошли несколько этапов клинических исследований. Для целого ряда ферментов показана противоопухолевая активность на доклиническом этапе в экспериментах in vivo: L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, биназа. В настоящем обзоре представлены ферменты, продемонстрировавшие на различных этапах исследований противоопухолевую активность, и перспективы их использования в онкогематологии.


Ключевые слова: противоопухолевые ферменты, L-аспарагиназа, L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, L-аргининдезиминаза, L-фенилаланин-аммиак-лиаза, ранпирназа.

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ЛИТЕРАТУРА

  1. Kidd J.G. Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum. J. Exp. Med. 1953; 98: 565–82.
  2. Broome J.D. Evidence that the L-asparaginase activity of guinea pig serum is responsible for its antilymphoma effects. Nature 1961; 191: 1114–5.
  3. Трещалина Е.М. Противоопухолевая активность веществ природного происхождения. М.: Практическая медицина, 2005. [Treshchalina Ye.M. Protivoopukholevaya aktivnost veshchestv prirodnogo proiskhozhdeniya (Anti-tumor activity of substances of natural origin). M.: Prakticheskaya meditsina, 2005.]
  4. Jaccard A., Petit B., Girault S. et al. L-asparaginase-based treatment of 15 western patients with extranodal NK/T-cell lymphoma and leukemia and a review of the literature. Ann Oncol. 2009; 20(1): 110–6.
  5. Obama K., Tara M., Niina K. L-asparaginase induced complete remission in Epstein-Barr virus positive, multidrug resistant, cutaneous T-cell lymphoma. Int. J. Hematol. 1999; 69(4): 260–2.
  6. Yong W., Zheng W., Zhang Y. et al. L-аsparaginase-based regimen in the treatment of refractory midline nasal/nasal-type T/NK-cell lymphoma. Int. J. Hematol. 2003; 78(2): 163–7.
  7. Ollenschlager G., Roth E., Linkesch W. et al. Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drugrelated side-effects. Eur. J. Clin Invest. 1988; 18(5): 512–6.
  8. Villa P., Corada M., Bartosek I. L-asparaginase effects on inhibition of protein synthesis and lowering of the glutamine content in cultured rat hepatocytes. Toxicol. Lett. 1986; 32(3): 235–41.
  9. Warrell R.P.Jr., Chou T.C., Gordon C. et al. Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults. Cancer Res. 1980; 40(12): 4546–51.
  10. Reinert R.B., Oberle L.M., Wek A.S. et al. Role of glutamine depletion in directing tissue-specific nutrient stress responses to L-asparagine. J. Biol. Chem. 2006; 281: 31222–33.
  11. Woods J.S., Handschumacher R.E. Hepatic homeostasis of plasma L-asparagine. Am. J. Physiol. 1971; 221: 1785–90.
  12. Bendich A., Kafkewitz D., Abuchowski A., Davis F.F. Immunological effects of native and polyethylene glycol-modified asparaginases from Vibrio succinogenes and Escherichia coli in normal and tumour-bearing mice. Clin. Exp. Immunol. 1982; 48: 273–8.
  13. Distasio J.A., Salazar A.M., Nadji M., Durden D.L. Glutaminase-free asparaginase from vibrio succinogenes: an antilymphoma enzyme lacking hepatotoxicity. Int. J. Cancer. 1982; 30(3): 343–7.
  14. Capizzy R.L., Cheng Y.C. Therapy of neoplasia with asparaginase. In: Enzymes as drug. Ed. by J.S. Holcenberg, J. Roberts. NY: John Wiley and Sons, 1981: 1–24.
  15. Storti E., Quaglino D. Dysmetabolic and neurological complications in leukemic patients treated with L-asparaginase. In: Experimental and clinical effects of L-asparaginase. Ed. by E. Grundmann, H.F. Oettgen. Berlin, Heidelberg, NY: Springer Verlag, 1970: 344–9.
  16. Roberts J., Schmid F.A., Old L.J., Stockert E. A comparative study of the antitumor effectiveness of E. coli and Erwinia asparaginases. Cancer Biochem. Biophys. 1976; 1(4): 175–8.
  17. Steiner M., Attarbaschi A., Kastner U. et al. Distinct fluctuations of ammonia levels during asparaginase therapy for childhood acute leukemia. Pediatr. Blood Cancer 2007; 9(5): 640–2.
  18. Watanabe S., Miyake K., Ogawa C. et al. The ex vivo production of ammonia predicts L-asparaginase biological activity in children with acute lymphoblastic leukemia. Int. J. Hematol. 2009; 90(3): 347–52.
  19. Гладилина Ю.А., Соколов Н.Н., Красоткина Ю.В. Клонирование, экспрессия и выделение L-аспарагиназы Helicobacter pylori. Биомед. хим. 2008; 54(4): С. 482–6. [Gladilina Yu.A., Sokolov N.N., Krasotkina Yu.V. Cloning, expression, and isolation of Helicobacter pylori L-asparaginase. Biomed. khim. 2008; 54(4): S. 482–6. (In Russ.)].
  20. Cappelletty D., Chiarelli L.R., Pasquetto M.V. et al. Helicobacter pylori L-asparaginase: A promising new chemotherapeutic agent. Biochem. Biophys. Res. Commun. 2008; 377: 1222–6.
  21. Derst C., Henseling J., R hm K.H. Engineering the substrate specificity of Escherichia coli asparaginase II. Selective reduction of glutaminase activity by amino acid replacements at position 248. Protein Sci. 2000; 9: 2009–17.
  22. Avramis V.I., Panosyan E.H. Pharmacokinetic/pharmacodynamic relationships of asparaginase formulations: the past, the present and recommendations for the future. Clin Pharmacokinet. 2005; 44: 367–93.
  23. Avramis V.I., Tiwari P.N. Asparaginase (native ASNase or pegylated ASNase) in the treatment of acute lymphoblastic leukemia. Int. J. Nanomed. 2006; 1(3): 241–54.
  24. Panosyan E.H., Grigoryan R.S., Avramis I.A. et al. Deamination of glutamine is a prerequisite for optimal asparagine deamination by asparaginases in vivo (CCG-1961). Anticancer Res. 2004; 24(2C): 1121–5.
  25. Rotoli B.M., Uggeri J., Dall’Asta V. et al. Inhibition of glutamine synthetase triggers apoptosis in asparaginase-resistant cells. Cell Physiol. Biochem. 2005; 15(6): 281–92.
  26. Tardito S., Uggeri J., Bozzetto C. et al. The inhibition of glutamine synthetase sensitizes human sarcoma cells to L-asparaginase. Cancer Chemother. Pharmacol. 2007; 60(5): 751–8.
  27. Abuchowski A., Kazo G.M., Verhoest C.R. Jr. et al. Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycolasparaginase conjugates. Cancer Biochem. Biophys. 1984; 7(2): 175–86.
  28. Asselin B.L., Whitin J.C., Coppola D.J. et al. Comparative pharmacokinetic studies of three asparaginase preparations. J. Clin. Oncol. 1993; 11: 1780–6. 29. Khan A., Hill J.M. Atopic hypersensitivity to L-asparaginase: resistance to immunosupression. Int. Arch. Allergy Appl. Immunol. 1971; 40(3): 463–569.
  29. Alvarez O.A., Zimmerman G. Pegaspargase-induced pancreatitis. Med. Pediatr. Oncol. 2000; 34(3): 200–5.
  30. Кучумова А.В., Красоткина Ю.В., Хасигов П.З., Соколов Н.Н. Пегили- рование рекомбинантной аспарагиназы Erwinia carotovora полиэтиленгликолем 5000. Биомед. хим. 2007; 53(1): 107–11. [Kuchumova A.V., Krasotkina Yu.V., Khasigov P.Z., Sokolov N.N. Pegylation of recombinant Erwinia carotovora asparaginase with polyethilenglycol. 5000. Biomed. khim. 2007; 53(1): 107–11. (In Russ.)].
  31. Gaspar M.M., Perez-Soler R., Cruz M.E. Biological characterization of L-asparaginase liposomal formulations. Cancer Chemother. Pharmacol. 1996; 38(4): 373–7.
  32. Jean-Francois J., D’Urso E.M., Fortier G. Immobilization of L-asparaginase into a biocompatible poly(ethylene glycol)-albumin hydrogel: evaluation of performance in vivo. Biotechnol. Appl. Biochem. 1997; 26(Pt. 3): 203–12.
  33. Gaspar M.M., Blanco D., Cruz M.E., Alonso M.J. Formulation of L-asparaginase load poly(lactide-to-glycolide) nanoparticles: influence of polymer properties on enzyme loading, activity and in vitro release. J. Control. Release 1998; 52: 53–62.
  34. Qian G., Zhou J., Wang D., He B. The chemical modification of E. coli L-asparaginase by N, O-carboxymethyl chitosan. Artif. Cell. Blood Substit. Immobil. Biotechnol. 1996; 24: 567–77.
  35. Uren J.R., Hargis B.J., Beardsley P. Immunological and pharmacological characterization of poly-DL-alanyl-modified Erwinia carotovora L-asparaginase. Cancer Res. 1982; 42: 4068–71.
  36. Jorge J.C., Perez-Soler R., Morais J.G., Cruz M.E. Liposomal palmitoylL-asparaginase: characterization and biological activity. Cancer Chemother. Pharmacol. 1994; 34(3): 230–4.
  37. Zhang Y.Q., Zhou W.L., Shen W.D. et al. Synthesis, characterization and immunogenicity of silk fibroin-L-asparaginase bioconjugates. J. Biotechnol. 2005; 120(3): 315–26.
  38. Leal-Egana A., Scheibel T. Silk-based materials for biomedical applications. Biotechnol. Appl. Biochem. 2010; 55(3): 155–67.
  39. Spiess K., Lammel A., Scheibel T. Recombinant spider silk proteins for applications in biomaterials. Macromol. Biosci. 2010; 10(9): 998–1007.
  40. Kwon Y.M., Chung H.S., Moon C. et al. L-Asparaginase encapsulated intact erythrocytes for treatment of acute lymphoblastic leukemia. J. Control. Release 2009; 139(3): 182–9.
  41. Moola Z.B., Scawen M.D., Atkinson T., Nicholls D.J. Erwinia chrysanthemi L-asparaginase: epitope mapping and production of antigenically modified enzymes. Biochem. J. 1994; 302(Pt. 3): 921–7.
  42. Goldberg A.I., Cooney D.A., Glynn J.P. et al. The effects of immunization to L-asparaginase on antitumor and enzymatic activity. Cancer Res. 1973; 33: 256–61.
  43. Vrooman L.M., Supko J.G., Neuberg D.S. et al. Erwinia asparaginase after allergy to E. coli asparaginase in children with acute lymphoblastic leukemia. Pediatr. Blood Cancer 2010; 54(2): 199–205.
  44. Zalewska-Szewczyk B., Gach A., Wyka K. et al. The cross-reactivity of anti-asparaginase antibodies against different L-asparaginase preparations. Clin. Exp. Med. 2009; 2: 113–6.
  45. Distasio J.A., Niederman R.A. Purification and characterization of Lasparaginase with anti-lymphoma activity from Vibrio succinogenes. J. Biol. Chem. 1976; 251(22): 6929–33.
  46. Абакумова О.Ю., Подобед О.В., Борисова А.А. и др. Противоопухолевая активность L-аспарагиназы из Yersinia pseudotuberculosis. Биомед. хим. 2008; 54(6): 712–9. [Abakumova O.Yu., Podobed O.V., Borisova A.A. et al. Anti-tumor activity of Yersinia pseudotuberculosis L-asparaginase. Biomed. khim. 2008; 54(6): 712–9. (In Russ.)].
  47. Carta De-Angeli L., Pocchiari F. et al. Effect of L-asparaginase from Aspergillus terreus on ascites sarcoma in the rat. Nature (London) 1970; 225: 549–50.
  48. Peterson L.E., Ciegler A. L-asparaginase production by Erwinia aroideae. Appl. Microbiol. 1969; 18: 64–7.
  49. Pritsa A.A., Papazisis K.T., Kortsaris A.H. et al. Antitumor activity of Lasparaginase from Thermus thermophilus. Anticancer Drugs 2001; 12: 137–42.
  50. Reddy V.V.S., Jayaram H.N., Sirsi M., Ramakrishnan T. Inhibitory activity of L-asparaginase from Mycobacterium tuberculosis on Yoshida ascites sarcoma in rats. Arch. Biochem. Biophys. 1969; 132: 262–7.
  51. Rowley B., Wriston J.C. Partial purification and antilymphoma activity of Serratia marcescens L-asparaginase. Biochem. Biophys. Res. Commun. 1967; 28: 160–5.
  52. Pokrovskaya M.V., Pokrovsky V.S., Aleksandrova S.S. et al. Recombinant intracellular Rhodospirillum riubrum L-asparaginase with low L-glutaminase activity and antiproliferative effect. Biochem. (Mosc.). Suppl. Series B: Biomed. Chem. 2012; 6: 121–31.
  53. Appel I.M., Hop W.C., Pieters R. Changes in hypercoagulability by asparaginase: a randomized study between two asparaginases. Blood Coagul. Fibrinol. 2006; 17: 139–46.
  54. Duval M., Suciu S., Ferster A. et al. Comparison of Escherichia coliasparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children’s Leukemia Group phase 3 trial. Blood 2002; 99(8): 2734–9.
  55. Durden D.L., Salazar A.M., Distasio J.A. Kinetic analisys of hepatotoxicity associated with antineoplastic asparaginases. Cancer Res. 1983; 43: 1602–5.
  56. Eden O.B., Shaw M.P., Lilleyman J.S., Richards S. Non-randomised study comparing toxicity of Escherichia coli and Erwinia asparaginase in children with leukaemia. Med. Pediatr. Oncol. 1990; 18(6): 497–502.
  57. Howard J.B., Carpenter F.H. L-asparaginase from Erwinia carotovora. Substrate specificity and enzymatic properties. J. Biol. Chem. 1972; 247: 1020–30.
  58. Bach S.J., Lasnitzki I. Some aspects of the role of arginine and arginase in mouse carcinoma 63. Enzymologia 1947; 12(3): 198–205.
  59. Bach S.J., Maw G.A. Creatine synthesis by tumor-bearing rats. Biochem. Biophys. Acta 1953; 11(1): 69–78.
  60. Osunkoya B.O., Adler W.H., Smith R.T. Effect of arginine deficiency on synthesis of DNA and immunoglobulin receptor of Burkitt lymphoma cells. Nature 1970; 227: 398–9.
  61. Storr J.M., Burton A.F. The effects of arginine deficiency on lymphoma cells. Br. J. Cancer 1974; 30: 50–9.
  62. Cheng P.N., Lam T.L., Lam W.M. et al. Pegylated recombinant human arginase inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion. Cancer Res. 2007; 67(1): 309–17.
  63. Savoca K.V., Davis F.F., van Es T. et al. Cancer therapy with chemically modified enzymes. II. The therapeutic effectiveness of arginase, and arginase modified by the covalent attachment of polyethylene glycol, on the taper liver tumor and the L5178Y murine leukemia. Cancer Biochem. Biophys. 1984; 7(3): 261–8.
  64. Hernandez C.P., Morrow K., Lopez-Barcons L.A. et al. Pegylated arginase I: a potential therapeutic approach in T-ALL. Blood 2010; 115(25): 5214–21.
  65. Hsueh E.C., Knebel S.M., Lo W.H. et al. Deprivation of arginine by recombinant human arginase in prostate cancer cells. J. Hematol. Oncol. 2012; 5: 17. doi: 10.1186/1756-8722-5-17.
  66. Shibatani T., Kakimoto T., Chibata I. Crystallization and properties of L-arginine deiminase of Pseudomonas putida. J. Biol. Chem. 1975; 250(12): 4580–3.
  67. Takaku H., Takase M., Abe S. et al. In vivo anti-tumor activity of arginine deiminase purified from Mycoplasma arginini. Int. J. Cancer. 1992; 51(2): 244–9.
  68. Park I.S., Kang S.W., Shin Y.J. et al. Arginine deiminase: a potential inhibitor of angiogenesis and tumour growth. Br. J. Cancer 2003; 89: 907–14.
  69. Ni Y., Li Z., Sun Z. et al. Expression of arginine deiminase from Pseudomonas plecoglossicida CGMCC2039 in Escherichia coli and its anti-tumor activity. Curr. Microbiol. 2009; 58(6): 593–8.
  70. Ensor C.M., Holtsberg F.W., Bomalaski J.S., Clark M.A. Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Cancer Res. 2002; 62: 5443–50.
  71. Gong H., Zolzer F., von Recklinghausen G. et al. Arginine deiminase inhibits proliferation of human leukemia cells more potently than asparaginase by inducing cell cycle arrest and apoptosis. Leukemia 2000; 14(5): 826–9.
  72. Noh E.J., Kang S.W., Shin Y.J. et al. Arginine deiminase enhances dexamethasone-induced cytotoxicity in human T-lymphoblastic leukemia CCRF-CEM cells. Int. J. Cancer 2004: 112: 502–8.
  73. Ascierto P.A., Scala S., Castello G. et al. Pegylated arginine deiminase treatment of patients with metastatic melanoma: results from phase I and II studies. J. Clin. Oncol. 2005; 23: 7660–8.
  74. Curley S.A., Bomalaski J.S., Ensor C.M. et al. Regression of hepatocellular cancer in a patient treated with arginine deiminase. Hepatogastroenterology 2003; 50(53): 1214–6.
  75. Glazer E.S., Piccirillo M., Albino V. et al. Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. J. Clin. Oncol. 2010; 28(13): 2220–6.
  76. Izzo F., Marra P., Beneduce G. et al. Pegylated arginine deiminase treatment of patients with unresectable hepatocellular carcinoma: results from phase I/II studies. J. Clin. Oncol. 2004; 22: 1815–22.
  77. Glazer E.S., Piccirillo M., Albino V. et al. Phase II study of pegylated arginine deiminase for nonresectable and metastatic hepatocellular carcinoma. J. Clin. Oncol. 2010; 28(13): 2220–6.
  78. Ott P.A., Carvajal R.D., Pandit-Taskar N. et al. Phase I/II study of pegylated arginine deiminase (ADI-PEG20) in patients with advanced melanoma. Invest. New Drugs 2013; 31(2): 425–34.
  79. Delage B., Luong P., Maharaj L. et al. Promoter methylation of argininosuccinate synthetase-1 sensitises lymphomas to arginine deiminase treatment, autophagy and caspase-dependent apoptosis. Cell Death Dis. 2012; 3: e342.
  80. Wu L., Li L., Meng S. et al. Expression of argininosuccinate synthetase in patients with hepatocellular carcinoma. J. Gastroenterol. Hepatol. 2013; 28(2): 365–8.
  81. Szlosarek P.W., Luong P., Phillips M.M. et al. Metabolic response to pegylated arginine deiminase in mesothelioma with promoter methylation of argininosuccinate synthetase. J. Clin. Oncol. 2013; 31(7): e111–3.
  82. Feun L.G., Marini A., Walker G. et al. Negative argininosuccinate synthetase expression in melanoma tumours may predict clinical benefit from arginine-depleting therapy with pegylated arginine deiminase. Br. J. Cancer 2012; 106(9): 1481–5.
  83. Kelly M.P., Jungbluth A.A., Wu B.W. et al. Arginine deiminase PEG20 inhibits growth of small cell lung cancers lacking expression of argininosuccinate synthetase. Br. J. Cancer 2012; 106(2): 324–32.
  84. Manca A., Sini M.C., Izzo F. et al. Induction of arginosuccinate synthetase (ASS) expression affects the antiproliferative activity of arginine deiminase (ADI) in melanoma cells. Oncol. Rep. 2011; 25(6): 1495–502.
  85. Bowles T.L., Kim R., Galante J. et al. Pancreatic cancer cell lines deficient in argininosuccinate synthetase are sensitive to arginine deprivation by arginine deiminase. Int. J. Cancer 2008; 123: 1950–5.
  86. Kim H.J., Kim J.H., Yu Y.S. et al. Anti-tumor activity of arginine deiminase via arginine deprivation in retinoblastoma. Oncol. Rep. 2007; 18: 1373–7.
  87. Kim R.H., Coates J.M., Bowles T.L. et al. Arginine deiminase as a novel therapy for prostate cancer induces autophagy and caspase-independent apoptosis. Cancer Res. 2009; 69: 700–8.
  88. Sigimura K., Ohno T., Kusuyama T., Azuma I. High sensitivity of human melanoma cell lines to the growth inhibitory activity of mycoplasmal arginine deiminase in vitro. Melanoma Res. 1992; 2: 191–6.
  89. Szlosarek P.W., Klabatsa A., Pallaska A. et al. In vivo loss of expression of argininosuccinate synthetase in malignant pleural mesothelioma is a biomarker for susceptibility to arginine depletion. Clin. Cancer Res. 2006; 12: 7126–31.
  90. Yoon C.Y., Shim Y.J., Kim E.H. et al. Renal cell carcinoma does not express argininosuccinate synthetase and is highly sensitive to arginine deprivation via arginine deiminase. Int. J. Cancer 2008; 120: 897–905.
  91. Tsai W.B., Aiba I., Lee S.Y. et al. Resistance to arginine deiminase treatment in melanoma cells is associated with induced argininosuccinate synthetase expression involving c-Myc/HIF-1alpha/Sp4. Mol. Cancer Ther. 2009; 8(12): 3223–33.
  92. Ni Y., Liu Y., Schwaneberg U. et al. Rapid evolution of arginine deiminase for improved anti-tumor activity. Appl. Microbiol. Biotechnol. 2011; 90(1): 193–201.
  93. Holtsberg F.W., Ensor C.M., Steiner M.R. et al. Poly(ethylene glycol) (PEG) conjugated arginine deiminase: effects of PEG formulations on its pharmacological properties. J. Control. Release 2002; 80: 259–71.
  94. Kreis W., Hession C. Biological effects of enzymatic deprivation of Lmethionine in cell culture and an experimental tumor. Cancer Res. 1973; 33(8): 1866–9.
  95. Занин В.А., Лукина В.И., Березов Т.Т. Выделение и некоторые фи- зико-химические и каталитические свойства L-лизин-альфа-оксидазы из Pseudomonas putida. Вопр. мед. хим. 1989; 4: 84–9. [Zanin V.A., Lukina V.I., Berezov T.T. Isolation and some physicochemical and catalytical properties of Pseudomonas putida L-lysine alpha-oxidase. Vopr. med. khim. 1989; 4: 84–9. (In Russ.)].
  96. Манухов И.В., Мамаева Д.В., Морозова Е.А. и др. L-Метионин-гамма- лиаза Citrobacter freundii: клонирование гена и кинетические параметры фермента. Биохим. 2006; 74(4): 454–63. [Manukhov I.V., Mamayeva D.V., Morozova Ye.A. et al. Citrobacter freundii L-methionine gamma-lyase: gene cloning and clinical parameters of enzyme. Biokhim. 2006; 74(4): 454–63. (In Russ.)].
  97. Ito S., Nakamura T., Eguchi Y. Purification and characterization of methioninase from Pseudomonas putida. J. Biochem. 1976; 79(6): 1263–72.
  98. Lockwood B.C., Coombs G.H. Purification and characterization of methionine gamma-lyase from Trichomonas vaginalis. Biochem. J. 1991; 279: 675–82.
  99. Sato D., Yamagata W., Kamei K. et al. Expression, purification and crystallization of L-methionine gamma-lyase 2 from Entamoeba histolytica. Acta Crystallogr. 2006; 62(10): 1034–6.
  100. Tanaka H., Esaki N., Yamamoto T., Soda K. Purification and properties of methioninase from Pseudomonas ovalis. FEBS Lett. 1976; 66(2): 307–11.
  101. El-Sayed A.S. Purification and characterization of a new L-methioninase from solid cultures of Aspergillus flavipes. J. Microbiol. 2011; 49(1): 130–40.
  102. Пехов А.А., Жукова О.С., Занин В.А., Березов Т.Т. Цитостатический эффект L-метионин-g-лиазы на раковые клетки в культуре. Бюл. эксп. биол. мед. 1983; 5: 87–9. [Pekhov A.A., Zhukova O.S., Zanin V.A., Berezov T.T. Cytostatic effect of L-methionine g-lyase on cultured cancer cells. Byul. eksp. biol. med. 1983; 5: 87–9. (In Russ.)].
  103. Hu J., Cheung N.K. Methionine depletion with recombinant methioninase: in vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drugs. Int. J. Cancer 2009; 124(7): 1700–6.
  104. Kokkinakis D.M., Schold S.C.Jr., Hori H., Nobori T. Effect of long-term depletion of plasma methionine on the growth and survival of human brain tumor xenografts in athymic mice. Nutr. Cancer 1997; 29(3): 195–204.
  105. Tan Y., Sun X., Xu M. et al. Efficacy of recombinant methioninase in combination with cisplatin on human colon tumors in nude mice. Clin. Cancer Res. 1999; 5(8): 2157–63.
  106. Tan Y., Xu M., Guo H. et al. Anticancer efficacy of methioninase in vivo. Anticancer Res. 1996; 16(6C): 3931–6.
  107. Yoshioka T., Wada T., Uchida N. et al. Anticancer efficacy in vivo and in vitro, synergy with 5-fluorouracil, and safety of recombinant methioninase. Cancer Res. 1998; 58(12): 2583–7.
  108. Hori H., Takabayashi K., Orvis L. et al Gene cloning and characterization of Pseudomonas putida L-methionine-alpha-deamino-gamma-mercaptomethane-lyase. Cancer Res. 1996; 56(9): 2116–22.
  109. El-Sayed A.S., Shouman S.A., Nassrat H.M. Pharmacokinetics, immunogenicity and anticancer efficiency of Aspergillus flavipes L-methioninase. Enzyme Microb. Technol. 2012; 51(4): 200–10.
  110. Tan Y., Zavala J.Sr., Xu M. et al. Serum methionine depletion without side effects by methioninase in metastatic breast cancer patients. Anticancer Res. 1996; 16(6C): 3937–42.
  111. Sun X., Yang Z., Li S. et al. In vivo efficacy of recombinant methioninase is enhanced by the combination of polyethylene glycol conjugation and pyridoxal 5¢-phosphate supplementation. Cancer Res. 2003; 63(23): 8377–83.
  112. Xin L., Cao J., Cheng H. et al. Stealth cationic liposomes modified with anti-CAGE single-chain fragment variable deliver recombinant methioninase for gastric carcinoma therapy. J. Nanosci. Nanotechnol. 2013; 13(1): 178–83.
  113. Смирнова И.П., Хадуев С.Х. L-лизин-альфа-оксидазная активность некоторых видов Trichoderma. Микробиология 1984; 53: 163–5. [Smirnova I.P., Khaduyev S.Kh. L-lysine alpha-oxidase activity of some Trichoderma spp. Mikrobiologiya 1984; 53: 163–5. (In Russ.)].
  114. Kusakabe H., Kodama K., Kuninaka A. et al. A new antitumor enzyme, L-lysine alpha-oxidase from Trichoderma viride. Purification and enzymological properties. J. Biol. Chem. 1980; 255(3): 976–81.
  115. Жукова О.С., Хадуев С.Х., Добрынин Я.В. и др. Влияние L-лизин-a- оксидазы на кинетику клеточного цикла культивируемых клеток лимфомы Беркитта. Экспер. онкол. 1985; 7(6): 42–4. [Zhukova O.S., Khaduyev S.Kh., Dobrynin Ya.V. et al. Influence of L-lysine a-oxidase on kinetics of cell cycle of Burkitt’s lymphoma cultured cells. Eksper. onkol. 1985; 7(6): 42–4. (In Russ.)].
  116. Гогичаева Н.В., Лукашева Е.В., Гаврилова Е.М. и др. Получение конъюгатов L-лизин-a-оксидазы с антителами. Вопр. мед. хим. 2000; 46(4): 410–8. [Gogichayeva N.V., Lukasheva Ye.V., Gavrilova Ye.M. et al. Synthesis of conjugates of L-lysine a-oxidase with antibodies. Vopr. med. khim. 2000; 46(4): 410–8. (In Russ.)].
  117. Лукашева Е.В., Березов Т.Т. L-лизин-a-оксидаза: физико-химиче- ские и биологические свойства. Биохимия 2002; 67(10): 1394–402. [Lukasheva Ye.V., Berezov T.T. L-lysine a-oxidase: physicochemical and biological properties. Biokhimiya 2002; 67(10): 1394–402. (In Russ.)].
  118. Sarkissian C.N., Shao Z., Blain F. et al. A different approach to treatment of phenylketonuria: phenylalanine degradation with recombinant phenylalanine ammonia lyase. Proc. Natl. Acad. Sci. U S A 1999; 96(5): 2339–44.
  119. Calabrese J.C., Jordan D.B., Boodhoo A. et al. Crystal structure of phenylalanine ammonia-lyase: multiple helix dipoles implicated in catalysis. Biochemistry 2004; 43: 11403–16.
  120. Ritter H., Schulz G.E. Structural basis for the entrance into the phenylpropanoid metabolism catalyzed by phenylalanine ammonia-lyase. Plant Cell 2004; 16: 3426–36.
  121. Bourget L., Chang T.M. Artificial cell-microencapsulated phenylalanine ammonia-lyase. Applied Biochem. Biotechnol. 1984; 10: 57–9.
  122. Sarkissian C.N., Gamez A. Phenylalanine ammonia lyase, enzyme substitution therapy for phenylketonuria, where are we now? Mol. Gen. Metab. 2005; 86(Suppl. 1): S22–6.
  123. Abell C.W., Hodgins D.S., Stith W.J. An in vivo evaluation of the chemotherapeutic potency of phenylalanine ammonia-lyase. Cancer Res. 1973; 33(10): 2529–32.
  124. Stith W.J., Hodgins D.S., Abell C.W. Effects of phenylalanine ammonialyase and phenylalanine deprivation on murine leukemic lymphoblasts in vitro. Cancer Res. 1973; 33(5): 966–71.
  125. Ambrus C.M., Anthone S., Horvath C. et al. Extracorporeal enzyme reactors for depletion of phenylalanine in phenylketonuria. Ann. Intern. Med. 1987; 106: 531–7.
  126. Ledoux L. Action of ribonuclease on two solid tumours in vivo. Nature 1955; 176(4470): 36–7.
  127. Mitkevich V.A., Tchurikov N.A., Zelenikhin P.V. et al. Binase cleaves cellular noncoding RNAs and affects coding mRNAs. FEBS J. 2010; 277(1): 186–96.
  128. Darzynkiewicz Z., Carter S.P., Mikulski S.M. et al. Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent. Cell Tissue Kinet. 1988; 21(3): 169–82.
  129. Ardelt W., Mikulski S.M., Shogen K. Amino acid sequence of an antitumor protein from Rana pipiens oocytes and early embryos. Homology to pancreatic ribonucleases. Biol. Chem. 1991; 266(1): 245–51.
  130. Wu Y., Mikulski S.M., Ardelt W. et al. A cytotoxic ribonuclease. Study of the mechanism of onconase cytotoxicity. J. Biol. Chem. 1993; 268(14): 10686–93.
  131. Juan G., Ardelt B., Li X. et al. G1 arrest of U937 cells by onconase is associated with suppression of cyclin D3 expression, induction of p16INK4A, p21WAF1/CIP1 and p27KIP and decreased pRb phosphorylation. Leukemia 1998; 12(8): 1241–8.
  132. Deptala A., Halicka H.D., Ardelt B. et al. Potentiation of tumor necrosis factor induced apoptosis by onconase. Int. J. Oncol. 1998; 13(1): 11–6.
  133. Lee I., Kalota A., Gewirtz A.M., Shogen K. Antitumor efficacy of the cytotoxic RNase, ranpirnase, on A549 human lung cancer xenografts of nude mice. Anticancer Res. 2007; 27(1A): 299–307.
  134. Lee I., Lee Y.H., Mikulski S.M., Shogen K. Effect of onconase +/- tamoxifen on ASPC-1 human pancreatic tumors in nude mice. Adv. Exp. Med. Biol. 2003; 530: 187–96.
  135. Воробьев И.И., Пономаренко Н.А., Дурова О.М. и др. Структурно- функциональное исследование рекомбинантных форм онконазы. Био- орган. хим. 2001; 27(4): 257–64. [Vorobyev I.I., Ponomarenko N.A., Durova O.M. et al. Structural-functional evaluation of Onconase recombinant forms. Bioorgan. khim. 2001; 27(4): 257–64. (In Russ.)].
  136. Notomista E., Cafaro V., Fusiello R. et al. Effective expression and purification of recombinant onconase, an antitumor protein. FEBS Lett. 1999; 463(3): 211–5.
  137. Ita M., Halicka H.D., Tanaka T. et al. Remarkable enhancement of cytotoxicity of onconase and cepharanthine when used in combination on various tumor cell lines. Cancer Biol Ther. 2008; 7(7): 1104–8.
  138. Costanzi J., Sidransky D., Navon A. et al. Ribonucleases as a novel pro-apoptotic anticancer strategy: review of the preclinical and clinical data for ranpirnase. Cancer Invest. 2005; 23(7): 643–50.
  139. Mikulski S.M., Costanzi J.J., Vogelzang N.J. et al. Phase II trial of a single weekly intravenous dose of ranpirnase in patients with unresectable malignant mesothelioma. J. Clin. Oncol. 2002; 20(1): 274–81.
  140. Porta C., Paglino C., Mutti L. Ranpirnase and its potential for the treatment of unresectable malignant mesothelioma. Biologics 2008; 2(4): 601–9.
  141. Chang C.H., Sapra P., Vanama S.S. et al. Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin. Blood 2005; 106(13): 4308–14.
  142. Calabrese J.C., Jordan D.B., Boodhoo A. et al. Crystal structure of phenylalanine ammonia-lyase: multiple helix dipoles implicated in catalysis. Biochemistry 2004; 43: 11403–16.
  143. Ardelt B., Ardelt W., Pozarowski P. et al. Cytostatic and cytotoxic properties of Amphinase: a novel cytotoxic ribonuclease from Rana pipiens oocytes. Cell Cycle 2007; 24: 3097–102.
  144. Ильинская О.Н., Зеленихин П.В., Колпаков А.И. и др. Избирательная цитотоксичность биназы в отношении фибробластов, экспрессирующих онкогены ras и AML/ETO. Учен. зап. Казан. ун-та. Серия «Естественные науки» 2008; 150(4): 268–73. [Ilinskaya O.N., Zelenikhin P.V., Kolpakov A.I. et al. Selective binase cytotoxicity against ras- and AML/ETO-oncogene-expressing fibroblasts. Uchen. zap. Kazan. un-ta. Seriya «Estestvennye nauki» 2008; 150(4): 268–73. (In Russ.)].
  145. Mitkevich V.A., Kretova O.V., Petrushanko I.Y. et al. Ribonuclease binase apoptotic signature in leukemic Kasumi-1 cells. Biochemie 2013; 95(6): 1344–9.
  146. Mitkevich V.A., Petrushanko I.Y., Spirin P.V. et al. Sensitivity of acute myeloid leukemia Kasumi-1 cells to binase toxic action depends on the expression of KIT and АML1-ETO oncogenes. Cell Cycle 2011; 10(23): 4090–7.