cancer

Anemia of Chronic Disease: Key Mechanisms of Pathogenesis in Patients with Malignancies and Feasible Classification Approaches

ANEMIAS , , , , , , ,

VT Sakhin1, ER Madzhanova1, EV Kryukov3, AV Sotnikov2, AV Gordienko2, OA Rukavitsyn3

1 1586 Military Clinical Hospital, 4 Mashtakova str., Moscow Region, Podolsk, Russian Federation, 142110

2 SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3 NN Burdenko Central Military Clinical Hospital, 3 Gospital’naya sq., Moscow, Russian Federation, 105229

For correspondence: Valerii Timofeevich Sakhin, MD, PhD, 4 Mashtakova str., Moscow Region, Podolsk, Russian Federation, 142110; Tel.: +7(916)314-31-11; e-mail: SahinVT@yandex.ru

For citation: Sakhin VT, Madzhanova ER, Kryukov EV, et al. Anemia of Chronic Disease: Key Mechanisms of Pathogenesis in Patients with Malignancies and Feasible Classification Approaches. Clinical oncohematology. 2019;12(3):344–9 (In Russ).

doi: 10.21320/2500-2139-2019-12-3-344-349

ABSTRACT

Aim. To study the effect of hepcidin, soluble transferrin receptor (sTfR), and cytokines on iron metabolism and occurrence of anemia in patients with malignancies and to propose, on this basis, a draft classification of anemia of chronic disease (ACD) based on the major pathogenic factor.

Materials & Methods. The trial included 63 patients with malignancies of stage II/IV: 41 patients with anemia (34 men, 7 women, mean age 67.1 ± 9.9 years), 22 patients without anemia (17 men, 5 women, mean age 60.2 ± 14.9 years). Comparative analysis was based on the values of iron metabolism, C-reactive protein (CRP), hepcidin, sTfR, as well as pro-inflammatory (interleukin-6 [IL-6], tumour necrosis factor α [TNF-α]) and anti-inflammatory (IL-10) cytokines in solid malignancy patients with and without anemia. The correlation analysis between IL-6, IL-10, TNF-α, hepcidin, sTfR, and blood count was performed.

Results. Compared with the control group patients with anemia show lower levels of iron concentration, total iron-binding capacity (TIBC), and percent transferrin saturation (TSAT), as well as higher level of CRP, hepcidin, sTfR, IL-6, IL-10, and TNF-α (p < 0.05). IL-6 (r = –0.58), TNF-α (r = –0.32), and hepcidin (r = –0.57) proved to negatively affect erythrocyte level. A negative correlation was established between hemoglobin concentration and IL-6 (r = –0.57), IL-10 (r = –0.64), TNF-α (r = –0.65), hepcidin (r = –0.3), and sTfR (r = –0.57). A correlation was identified between concentrations of hepcidin and IL-6 (r = 0.58), IL-10 (r = 0.33), TNF-α (r = –0.4), as well as between concentrations of sTfR and IL-10 (r = 0.58), TNF-α (r = –0.53). A relationship was identified between IL-6 concentration and iron status (r = –0.38), TIBC (r = –0.56), TSAT (r = –0.31), ferritin (r = 0.56), transferrin (r = –0.72), CRP (r = 0.86) as well as between concentrations of IL-10 and iron (r = –0.63), TSAT (r = –0.67), transferrin (r = –0.7), ferritin (r = 0.55), CRP (r = 0.65), TIBC (r = –0.71). A correlation between the levels of TNF-α and TIBC (r = –0.36), transferrin (r = –0.5) was confirmed.

Conclusion. The paper deals with multi-factorial pathogenesis of anemia in patients with malignancies. Most important factors are iron deficiency and erythropoietic disorder. A draft ACD classification based on the major pathogenic factor of anemia (ACD with dominating iron deficiency, ACD with impaired regulatory mechanism of erythropoiesis, and ACD with insufficient erythropoietin production) is proposed.

Keywords: cancer, anemia, iron metabolism, interleukin-6, interleukin-10, tumor necrosis factor alpha, hepcidin, soluble transferrin receptor.

Received: January 21, 2019

Accepted: June 18, 2019

Read in PDF 

REFERENCES

  1. Weiss G. Pathogenesis and treatment of anaemia of chronic disease. Blood Rev. 2002;16(2):87–96. doi: 10.1054/blre.2002.0193.

  2. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23. doi: 10.1056/nejmra041809.

  3. Means RT. Recent developments in the anemia of chronic disease. Curr Hematol Rep. 2003;2(2):116–21.

  4. Poggiali E, De Amicis MM, Motta I, et al. Anemia of chronic disease: a unique defect of iron recycling for many different chronic diseases. Eur J Int Med. 2014;25(1):12–17. doi: 10.1016/j.ejim.2013.07.011.

  5. Weiss G. Iron metabolism in the anemia of chronic disease. Biochim Biophys Acta. 2009;1790(7):682–93. doi: 10.1016/j.bbagen.2008.08.006.

  6. Ganz T, Nemeth E. Hepcidin and iron homeostasis. Biochim Biophys Acta. 2012;1823(9):1434–43. doi: 10.1016/j.bbamcr.2012.01.014.

  7. McCranor BJ, Kim MJ, Cruz NM, et al. Interleukin-6 directly impairs the erythroid development of human TF-1 erythroleukemic cells. Blood Cells Mol Dis. 2014;52(2–3):126–33. doi: 10.1016/j.bcmd.2013.09.004.

  8. Анемии. Под ред. О.А. Рукавицына. 2-е изд., перераб. и доп. М.: ГЭОТАР-Медиа, 2016. 256 c.

    [Rukavitsyn OA, ed. (Anemias.) 2nd revised edition. Moscow: GEOTAR-Media Publ.; 2016. 256 p. (In Russ)]

  9. Сахин В.Т., Маджанова Е.Р., Крюков Е.В. и др. Анемия хронических заболеваний: особенности патогенеза и возможности терапевтической коррекции (обзор литературы и результаты собственных исследований). Онкогематология. 2018;13(1):45–53. doi: 10.17650/1818-8346-2018-13-1-45-53.

    [Sakhin VТ, Madzhanova ЕR, Kryukov EV, et al. Anemia of chronic disease: features of pathogenesis and possible therapeutic correction (literature review and results of own research). Oncohematology. 2018;13(1):45–53. doi: 10.17650/1818-8346-2018-13-1-45-53. (In Russ)]

  10. Steinmetz T, Totzke U, Schweigert M, et al. A prospective observational study of anaemia management in cancer patients–results from the German Cancer Anaemia Registry. Eur J Cancer Care. 2011;20(4):493–502. doi: 10.1111/j.1365-2354.2010.01230.x.

  11. Waters JS, O’Brien MER, Ashley S. Management of anemia in patients receiving chemotherapy. J Clin Oncol. 2002;20(2):601–3. doi: 10.1200/JCO.2002.20.2.601.

  12. Grotto HZ. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Med Oncol. 2008;25(1):12–21. doi: 1007/s12032-007-9000-8.

  13. Гематология: национальное руководство. Под ред. О.А. Рукавицына. М.: ГЭОТАР-Медиа, 2015. С. 143–9.

    [Rukavitsyn OA, ed. Gematologiya: natsional’noe rukovodstvo. (Hematology: national guidelines.) Moscow: GEOTAR-Media Publ.; 2015. pp. 143–9. (In Russ)]

  14. Steinmetz HT, Tsamaloukas A, Schmitz S, et al. A new concept for the differential diagnosis and therapy of anaemia in cancer patients. Support Care Cancer. 2010;19(2):261–9. doi: 10.1007/s00520-010-0812-2.

  15. Maccio A, Madeddu C, Massa D, et al. Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia. 2005;106(1):362–7. doi: 10.1182/blood-2005-01-0160.

  16. Сахин В.Т., Маджанова Е.Р., Крюков Е.В. и др. Патогенетические особенности анемии у больных с солидными опухолями. Клиническая онкогематология. 2017;10(4):514–8. doi: 10.21320/2500-2139-2017-10-4-514-518.

    [Sakhin VT, Madzhanova ER, Kryukov EV, et al. Pathogenetic Characteristics of Anemia in Patients with Solid Tumors. Clinical oncohematology. 2017;10(4):514–8. doi: 10.21320/2500-2139-2017-10-4-514-518. (In Russ)]

  17. Park S, Jung CW, Kim K, et al. Iron deficient erythropoiesis might play key role in development of anemia in cancer patients. Oncotarget. 2015;6(40):42803–12. doi: 10.18632/oncotarget.5658.

  18. Speeckaert MM, Speeckaert R, Delanghe JR. Biological and clinical aspects of soluble transferrin receptor. Crit Rev Clin Lab Sci. 2010;47(5–6):213–28. doi: 10.3109/10408363.2010.550461.

  19. Moldawer LL, Marano MA, Wei H, et al. Cachectin/tumor necrosis factor-alpha alters red blood cell kinetics and induces anemia in vivo. FASEB J. 1989;3(5):1637–43.

  20. Raj DSC. Role of interleukin-6 in the anemia of chronic disease. Sem Arthritis Rheum. 2009;38(5):382–8. doi: 10.1016/j.semarthrit.2008.01.006.

  21. Wrighting DM, Andrews NC. Interleukin-6 induces hepcidin expression through STAT3. Blood. 2006;108(9):3204–9. doi: 10.1182/blood-2006-06-027631.

  22. Huang P, Wang J, Lin X, et al. Effects of IL-10 on iron metabolism in LPS-induced inflammatory mice via modulating hepcidin expression. Eur Rev MedPharmacol Sci. 2017;21(15):3469–75.

  23. Shanmugam NKN, Ellenbogen S, Trebicka E, et al. Tumor necrosis factor α inhibits expression of the iron regulating hormone hepcidin in murine models of innate colitis. PLoS One. 2012;7(5):e38136. doi: 10.1371/journal.pone.0038136.

  24. De Lurdes Cabrita AA, Pinho A, Malho A, et al. Risk factors for high erythropoiesis stimulating agent resistance index in pre-dialysis chronic kidney disease patients, stages 4 and 5. Int Urol Nephrol. 2011;43(3):835–40. doi: 10.1007/s11255-010-9805-9.

  25. Nazemian F, Karimi G, Moatamedi M, et al. Effect of silymarin administration on TNFalpha serum concentration in peritoneal dialysis patients. Phytother Res. 2010;24(11):1654–7. doi: 10.1002/ptr.3175.

Pathogenetic Characteristics of Anemia in Patients with Solid Tumors

ANEMIAS , , , ,

VT Sakhin1, ER Madzhanova1, EV Kryukov3, AV Sotnikov2, AV Gordienko2, OA Rukavitsyn3

11586 Military Clinical Hospital, 4 Mashtakova str., Podolsk, Russian Federation, 142110

2SM Kirov Military Medical Academy, 6 Akademika Lebedeva str., Saint Petersburg, Russian Federation, 194044

3NN Burdenko Main Military Clinical Hospital, 3 Gospitalnaya sq., Moscow, Russian Federation, 105229

For correspondence: Valery Timofeevich Sakhin, PhD, 4 Mashtakova str., Podolsk, Russia, 142110; Tel.: +7(916)314-31-11; e-mail: SahinVT@yandex.ru

For citation: Sakhin VT, Madzhanova ER, Kryukov EV, et al. Pathogenetic Characteristics of Anemia in Patients with Solid Tumors. Clinical oncohematology. 2017;10(4):514–8 (In Russ).

DOI: 10.21320/2500-2139-2017-10-4-514-518

ABSTRACT

Aim. To study the impact iron metabolism disturbances and cytokine levels on the development of anemia in patients with solid tumors.

Materials & Methods. The research included 42 patients with malignant neoplasms, including 24 patients with anemia (19 men and 5 women, median age 67.7 ± 10 years) and 18 patients without anemia (15 men, 3 women, median age 65.7 ± 14 years). Anemia was diagnosed according to the WHO criteria (in men: erythrocytes < 4.0 × 1012/L, hemoglobin < 130 g/L, hematocrit < 39 %; in women: erythrocytes < 3.8 × 1012/L, hemoglobin < 120 g/L, hematocrit < 36 %).

Results. A comparative analysis of iron metabolism in patients with and without anemia was performed. The lower values of serum iron and transferrin saturation in patients with anemia were shown (p < 0.05). The total iron-binding capacity, the levels of ferritin, transferrin, C-reactive protein, indirect bilirubin were similar between groups (p > 0,05). Higher levels of interleukins 6 and 10 (IL-6 and IL-10) were observed in patients with anemia (p < 0.05). For IL-6, correlations were observed with levels of erythrocytes (r = –0,58), hemoglobin (r = –0,57), hematocrit (r = –0,52), and leukocytes (r = 0,42). The levels of IL-10 slightly correlated with the levels of erythrocytes, leukocytes, platelets, MCV, and MCH (r < 0.3). For IL-10, correlations were established with levels of MCHC (r = –0,71), hemoglobin (r = –0,64) and hematocrit (r = –0,32). Correlations between the levels IL-6, IL-6 and hemoglobin, erythrocytes and several color indices may indicate their influence on the development of anemia in patients with malignant neoplasms.

Conclusion. A functional iron deficiency in patients with anemia was found. Several causes of anemia development and significant role of interleukins in anemia pathogenesis were also discovered.

Keywords: cancer, anemia, iron metabolism, interleukin-6, interleukin-10.

Received: March 21, 2017

Accepted: June 22, 2017

Read in PDF

REFERENCES

  1. Maccio A, Madeddu C, Gramignano G, et al. The role of inflammation, iron, and nutritional status in cancer-related anemia: results of a large, prospective, observational study. Haematologica. 2015;100(1):124–32. doi: 10.3324/haematol.2014.112813.
  2. Ludwig H, Van Belle S, Barrett-Lee P, et al. The European Cancer Anaemia Survey (ECAS): A large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer. 2004;40(15):2293–306. doi: 10.1016/j.ejca.2004.06.019.
  3. Steinmetz T, Totzke U, Schweigert M, et al. A prospective observational study of anaemia management in cancer patients–results from the German Cancer Anaemia Registry. Eur J Cancer Care. 2011;20(4):493–502. doi: 10.1111/j.1365-2354.2010.01230.x.
  4. Waters JS, O’Brien MER, Ashley S. Management of anemia in patients receiving chemotherapy. J Clin Oncol. 2002;20(2):601–3. doi: 10.1200/JCO.2002.20.2.601.
  5. Grotto HZ. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Med Oncol. 2008;25(1):12–21. doi: 10.1007/s12032-007-9000-8.
  6. Гематология: национальное руководство. Под ред. О.А. Рукавицына. М.: ГЭОТАР-Медиа, 2015. С. 143–9.[Rukavitsyn OA, ed. Gematologiya: natsional’noe rukovodstvo. (Hematology: national guidelines.) Moscow: GEOTAR-Media Publ.; 2015. pp. 143–9 (In Russ)]
  7. Ludwig H, Muldur E, Endler G, et al. Prevalence of iron deficiency across different tumors and its association with poor performance status, disease status and anemia. Ann Oncol. 2013;24(7):1886–92. doi: 10.1093/annonc/mdt118.
  8. de Castro J, Gascоn P, Casas A, et al. Iron deficiency in patients with solid tumours: prevalence and management in clinical practice. Clin Transl Oncol. 2014;16(9):823–8. doi: 10.1007/s12094-013-1155-5.
  9. Beguin Y. Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica. 2002;87(11):1209–21.
  10. Steinmetz HT, Tsamaloukas A, Schmitz S, et al. A new concept for the differential diagnosis and therapy of anaemia in cancer patients. Support Care Cancer. 2010;19(2):261–9. doi: 10.1007/s00520-010-0812-2.
  11. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23. doi: 10.1056/nejmra041809.
  12. Maccio A, Madeddu C, Massa D, et al. Hemoglobin levels correlate with interleukin-6 levels in patients with advanced untreated epithelial ovarian cancer: role of inflammation in cancer-related anemia. Blood. 2005;106(1):362–7. doi: 10.1182/blood-2005-01-0160.
  13. Falkensammer CE, Thurnher M, Leonhartsberger N, Ramoner R. C-reactive protein is a strong predictor for anaemia in renal cell carcinoma: role of IL-6 in overall survival. BJU Int. 2011;107(12):1893–8. doi: 10.1111/j.1464-410x.2010.09817.x.

Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy

REVIEWS , , , , , ,

VS Pokrovskii1, DZh Davydov1, NV Anufrieva2, DD Zhdanov3, EM Treshchalina1, TV Demidkina2, EA Morozova2

1 NN Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

2 VA Engelhardt Institute of Molecular Biology, 32 Vavilova str., Moscow, Russian Federation, 119991

3 VN Orekhovich Institute of Biomedical Chemistry, 10 bld. 8 Pogodinskaya str., Moscow, Russian Federation, 119121

For correspondence: Vadim Sergeevich Pokrovskii, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: 8(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

For citation: Pokrovskii VS, Davydov DZh, Anufrieva NV, et al. Pathological Metabolism of Methionine in Malignant Cells Is a Potential Target for the Antitumor Therapy. Clinical oncohematology. 2017;10(3):324–32 (In Russ).

DOI: 10.21320/2500-2139-2017-10-3-324-332

ABSTRACT

This review presents the characteristics of the cellular metabolism of methionine, as well as known data on the mechanisms of the development of methionine dependence in malignant cells. The possibilities of using a non-methionine diet for the control of the tumor growth in patients with various forms of cancer are considered. The newest information about methionine-γ-lyase, an enzyme providing elimination of methionine from plasma, is grouped and summarised. Its role as a potential antitumor enzyme is disclosed. Data on methionine-γ-lyase producers, activity of this enzyme, obtained from various sources, and information on tumor models and cell cultures, showing methionine dependence are summarised.

Keywords: methionine-γ-liase, methionine, methionine dependency, cancer cells, cancer, anticancer enzymes, antitumor therapy.

Received: December 16, 2016

Accepted: March 6, 2017

Read in PDF (RUS)pdficon

REFERENCES

  1. Thomas D, Surdin-Kerjan Y. Metabolism of sulfur amino acids in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1997;61(4):503–32.
  2. Ravanel S, Gaki B, Job D, Douce R. The specific features of methionine biosynthesis and metabolism in plants. Proc Natl Acad Sci USA. 1998;95(13):7805–12. doi: 10.1073/pnas.95.13.7805.
  3. Sekowska A, Kung H, Danchin A, et al. Sulfur metabolism in Escherichia coli and related bacteria: facts and fiction. J Mol Microbiol Biotechnol. 2000;2(2):145–77.
  4. Guedes RL, Prosdocimi F, Fernandes GR, et al. Amino acids biosynthesis and nitrogen assimilation pathways: A great genomic deletion during eukaryotes. BMC Genom. 2011;12(Suppl 4):S2. doi: 10.1186/1471-2164-12-S4-S2.
  5. Satishchandran C, Taylor JC, Markham GD, et al. Novel Escherichia coli K-12 mutants impaired in S-adenosylmethionine synthesis. J Bacteriol. 1990;172(8):4489–96. doi: 10.1128/jb.172.8.4489-4496.1990.
  6. Zingg JM. Genetic and epigenetic aspects of DNA methylation on genome expression, evolution, mutation and carcinogenesis. Carcinogenesis. 1997;18(5):869–82. doi: 10.1093/carcin/18.5.869.
  7. Krasinskas A, Bartlett DL, Cieply K, et al. CDKN2A and MTAP deletions in peritoneal mesotheliomas are correlated with loss of p16 protein expression and poor survival. Mod Pathol. 2010;23(4):531–8. doi: 10.1038/modpathol.2009.186.
  8. Roje S. S-Adenosyl-L-methionine: Beyond the universal methyl group donor. Phytochemistry 2006;67(15):1686-1698. doi: 10.1016/j.phytochem.2006.04.019.
  9. Anderson ME. Glutatione: an overview of biosynthesis and modulation. Chem Biol Interact. 1998;111(112):1–14. doi: 10.1016/s0009-2797(97)00146-4.
  10. Thomas T, Tomas TJ. Polyamines in cell growth and cell death: molecular mechanisms and therapeutic applications. Cell Mol Life Sci. 2001;58(2):244–58. doi: 10.1007/PL00000852.
  11. Pirkov I, Norbeck J, Gustafsson L, et al. A complete inventory of all enzymes in the eukaryotic methionine salvage pathway. FEBS J. 2008;275(16):4111–20. doi: 10.1111/j.1742-4658.2008.06552.x.
  12. Quash G, Roch AM, Chantepie J, et al. Methional derived from 4-methylthio-2-oxobutanoate is a cellular mediator of apoptosis in BAF3 lymphoid cells. Biochem J. 1995;305(3):1017–25. doi: 10.1042/bj3051017.
  13. Bassila C, Ghemrawi R, Flayac J, et al. Methionine synthase and methionine synthase reductase interact with MMACHC and with MMADHC. Biochim Biophys Acta. 2017;1863(1):103–12. doi: 10.1016/j.bbadis.2016.10.016.
  14. Морозова Е.А., Куликова В.В., Яшин Д.В. и др. Кинетические характеристики и цитотоксическая активность рекомбинантных препаратов метионин–гамма-лиазы Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis и Citrobacter freundii. Acta Naturae. 2013;5:54–60.
    [Morozova EA, Kulikova VV, Yashin DV, et al. Kinetic parameters and cytotoxic activity of recombinant methionine γ-lyase from Clostridium tetani, Clostridium sporogenes, Porphyromonas gingivalis and Citrobacter freundii. Acta Naturae. 2013;5:54–60. (In Russ)]
  15. Cavuoto P, Fenech MF. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 2012;38(6):726–36. doi: 10.1016/j.ctrv.2012.01.004.
  16. Sugimura T, Birnbaum SM, Winitz M, et al. Quantitative nutritional studies with water-soluble, chemically defined diets. VIII. The forced feeding of diets each lacking in one essential amino acid. Arch Biochem Bioophys. 1959;81(2):448–55. doi: 10.1016/0003-9861(59)90225-5.
  17. Buch L, Streeter D, Halpern RM, et al. Inhibition of transfer ribonucleic acid methylase activity from several human tumors by nicotinamide and nicotinamide analogs. Biochemistry. 1972;11(3):393–7. doi: 10.1021/bi00753a015.
  18. Halpern BC, Clark BR, Hardy DN, et al. The effect of replacement of methionine by homocystine on survival of malignant and normal adult mammalian cells in culture. Proc Natl Acad Sci USA. 1974;71(4):1133–6. doi: 10.1073/pnas.71.4.1133.
  19. Judde JG, Ellis M, Frost P, et al. Biochemical analysis of the role of transmethylation in the methionine dependence of tumor cells. Cancer Res. 1989;49(17):4859–65.
  20. Hoffman RM, Jacobsen J. Reversible growth arrest in simian virus 40-transformed human fibroblasts. Proc Natl Acad Sci USA. 1980;77(12):7306–10. doi: 10.1073/pnas.77.12.7306.
  21. Guo H, Lishko VK, Herrera H, et al. Therapeutic tumor-specific cell cycle block induced by methionine starvation in vivo. Cancer Res. 1993;53(23):5676–9.
  22. Breillout F, Antoine E, Poupon MF. Methionine dependency of malignant tumors: a possible approach for therapy. J Natl Cancer Inst. 1990;82(20):1628–32. doi: 10.1093/jnci/82.20.1628.
  23. Lu S, Epner DE. Molecular mechanisms of cell cycle block by methionine restriction in human prostate cancer cells. Nutr Cancer. 2000;38(1):123–30. doi: 10.1207/S15327914NC381_17.
  24. Poirson-Bichat F, Goncalves RA, Miccoli L, et al. Methionine depletion enhances the antitumoral efficacy of cytotoxic agents in drug-resistant human tumor xenografts. Cancer Res. 2000;6(2):643–53.
  25. Guo H, Herrera H, Groce A, et al. Expression of the biochemical defect of methionine dependence in fresh patient tumors in primary histoculture. Cancer Res. 1993;53(11):2479–83.
  26. Kim DH, Muto M, Kuwahara Y, et al. Array-based comparative genomic hybridization of circulating esophageal tumor cells. Oncol Rep. 2006;16(5):1053–9. doi: 10.3892/or.16.5.1053.
  27. Poirson-Bichat F, Gonfalone G, Bras-Gone RA, et al. Growth of methionine dependent human prostate cancer (PC-3) is inhibited by ethionine combined with methionine starvation. Br J Cancer. 1997;75(11):1605–12. doi: 10.1038/bjc.1997.274.
  28. Jo YK, Park MH, Choi H, et al. Enhancement of the Antitumor Effect of Methotrexate on Colorectal Cancer Cells via Lactate Calcium Salt Targeting Methionine Metabolism / Nutr Cancer. 2017;69(4):663–73. doi: 10.1080/01635581.2017.1299879.
  29. Kreis W, Goodenow M. Methionine requirement and replacement by homocysteine in tissue cultures of selected rodent and human malignant and normal cells. Cancer Res. 1978;38(8):2259–62.
  30. Kennelly JC, Blair JA, Pheasant AE. Metabolism of 5-methyltetrahydrofolate by rats bearing the Walker 256 carcinosarcoma. Br J Cancer. 1982;46(3):440–3. doi: 10.1038/bjc.1982.222.
  31. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Investig Med. 1998;21(3):151–8.
  32. Bergstrom M, Ericson K, Hagenfeldt L, et al. PET study of methionine accumulation in glioma and normal brain tissue: competition with branched chain amino acids. J Comput Assist Tomogr. 1987;11(2):208–13. doi: 10.1097/00004728-198703000-00002.
  33. Stern PH, Hoffman RM. Elevated overall rates of transmethylation in cell lines from diverse human tumors. In Vitro. 1984;20(8):663–73. doi: 10.1007/bf02619617.
  34. Hoffman RM. Altered methionine metabolism and transmethylation in cancer. Anticancer Res. 1985;5(1):1–30.
  35. Давыдов Д.Ж., Морозова Е.А., Ануфриева Н.В. и др. Динамика содержания метионина в плазме крови мышей после введения метионин-гамма-лиазы. Российский биотерапевтический журнал. 2017;16(Suppl 1):28–9.
    [Davydov DZh, Morozova EA, Anufrieva NV, et al. The changes in plasma methionin concentrations in mice after methionine-gamma-lyase injection. Rossiiskii bioterapevticheskii zhurnal. 2017;16(Suppl 1):28–9. (In Russ)]
  36. Hoffman RM. Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesis: a review and synthesis. Biochim Biophys Acta. 1983;738(1–2):49–87. doi: 10.1016/0304-419x(84)90019-2.
  37. de Oliveira SF, Ganzinelli M, Chila R, et al. Characterization of MTAP Gene Expression in Breast Cancer Patients and Cell Lines. PLoS One. 2016;11(1):e0145647. doi: 10.1371/journal.pone.0145647.
  38. Nobori T, Karras JG, Della Ragione F, et al. Absence of methilthioadenosine phosphorylase in human gliomas. Cancer Res. 1991;51(12):3193–7.
  39. Schmid M, Malicki D, Nobori T, et al. Homozygous deletions of methilthioadenosine phosphorylase (MTAP) are more frequent then p16INK4A (CDKN2) homozygous deletions in primary non-small cell lung cancer (NSCLC). Oncogene. 1998;17(20):2669–75. doi: 10.1038/sj.onc.1202205.
  40. M’soka TJ, Nishioka J, Taga A, et al. Detection of methylthioadenosine phosphorylase (MTAP) and p16 gene deletion in T cell acute lymphoblastic leukemia by real-time quantitative PCR assay. Leukemia. 2000;14(5):935–40. doi: 10.1038/sj.leu.2401771.
  41. Garcia-Castellano JM, Villanueva A, Healey JH, et al. Methylthioadenosine phosphorylase gene deletions are common in osteosarcoma. Clin Cancer Res. 2002;8(3):782–7.
  42. Behrmann I, Wallner S, Komyod W, et al. Characterization of methylthioadenosin phosphorylase (MTAP) expression in malignant melanoma. Am J Pathol. 2003;162(2):683–90. doi: 10.1016/S0002-9440(10)63695-4.
  43. Komatsu A, Nagasaki K, Fujimori M, et al. Identification of novel deletion polymorphisms in breast cancer. Int J Oncol. 2008;33(2):261–70.
  44. Nobori T, Miura K, Wu DJ, et al. Deletions of the cyclin-dependent kinase-4 inhibitor gene in multiple human cancers. Nature. 1994;368(6473):753–6. doi: 10.1038/368753a0.
  45. Nobori T, Takabayashi K, Tran P, et al. Genomic cloning of methylthioadenosine phosphorylase: a purine metabolic enzyme deficient in multiple different cancers. Proc Natl Acad Sci USA. 2000;93(12):6203–8. doi: 10.1073/pnas.93.12.6203.
  46. Brat DJ, James CD, Jedlicka AE, et al. Molecular genetic alterations in radiation-induced astrocytomas. Am J Pathol. 1999;154(5):1431–8. doi: 10.1016/S0002-9440(10)65397-7.
  47. Christopher SA, Diegelman P, Porter CW, et al. Methylthioadenosine phosphorylase, a gene frequently codeleted with p16(cdkN2a/ARF), acts as a tumor suppressor in a breast cancer cell line. Cancer Res. 2002;62(22):6639–44.
  48. Jagasia AA, Block JA, Diaz MO, et al. Partial deletions of the CDKN2A and MTS2 putative tumor suppressor genes in a myxoid chondrosarcoma. Cancer Lett. 1996:105(1):77–90. doi: 10.1016/0304-3835(96)04273-5.
  49. Jagasia AA, Block JA, Qureshi A, et al. Chromosome 9 related aberration and deletions of the CDKN2 and MTS2 putative tumor suppressor genes in human chondrosarcomas. Cancer Lett. 1996;105(1):91–103. doi: 10.1016/0304-3835(96)04274-7.
  50. Powel EL, Leoni LM, Canto MI, et al. Concordant loss of MTAP and p16/CDKN2A expression in gastroesophageal carcinogenesis: evidence of homozygous deletion in esophageal noninvasive precursor lesions and therapeutic implications. Am J Surg Phatol. 2005;29(11):1497–504. doi: 10.1097/01.pas.0000170349.47680.e8.
  51. Kim J, Kim MA, Min SY, et al. Downregulation of methylthioadenosin phosphorylase by homozygous deletion in gastric carcinoma. Genes Chromos Cancer. 2011;50(6):421–33. doi: 10.1002/gcc.20867.
  52. Huang H-Y, Li S-H, Yu S-C, et al. Homozygous deletion of MTAP gene as a poor prognosticator in gastrointestinal stromal tumors. Clin Cancer Res. 2009;15(22):6963–72. doi: 10.1158/1078-0432.CCR-09-1511.
  53. Suzuki T, Maruno M, Wada K, et al. Genetic analysis of human glioblastomas using a genomic microarray system. Brain Tumor Pathol. 2004;21(1):27–34. doi: 10.1007/bf02482174.
  54. Zhang H, Chen ZH, Savarese TM, et al. Codeletion of the genes for p16INK4 methihthioadenosine phosphorylase, interferon-alpha1, interferon-beta1, and other 9p21 markers in human malignant cell lines. Cancer Genet Cytogenet. 1996;86(1):22–8. doi: 10.1016/0165-4608(95)00157-3.
  55. Perry A, Nobory T, Ru N, et al. Detection of p16 gene deletions in gliomas: comparison of fluorescence in situ hybridization (FISH) versus quantitative PCR. J Neuropathol Exp Neurol. 1997;56(9):999–1008. doi: 10.1097/00005072-199709000-00005.
  56. Orentreich N, Matias JR, DeFelice A, Zimmerman JA. Low methionine ingestion by rats extends life span . J Nutr. 1993;123(2):269–74.
  57. Efferth DE, Miyachi H, Drexler HG, Gebhart E. Methionine phosphorylase as target for chemoselective treatment of T-cell acute lymphoblastic leukemic cells. Blood Cells Mol Dis. 2002;28(1):47–56. doi: 10.1006/bcmd.2002.0483.
  58. Bertin R, Acquaviva C, Mirebeau D, et al. CDKN2A, CDKN2B and MTAP gene dosage permits precise characterization of mono- and bi-allelic 9p21 deletions in childhood acute lymphoblastic leukemia. Genes Chromos Cancer. 2003;37(1):44–57. doi: 10.1002/gcc.10188.
  59. Usvasalo A, Ninomiya S, Raty R, et al. Focal 9p instability in hematologic neoplasias revealed by comparative genomic hybridization and single-nucleotide polymorphism microarray analyses. Genes Chromos Cancer. 2010;49(4):309–18. doi: 10.1002/gcc.20741.
  60. Kamath A, Tara H, Xiang B, et al. Double-minute MYC amplification and deletion of MTAP, CDKN2A, CDKN2B and ELAVL2 in an acute myeloid leukemia characterized by oligonucleotide-array comparative genomic hybridization. J Cancer Genet Cytogenet. 2008;183(2):117–20. doi: 10.1016/j.cancergencyto.2008.02.011.
  61. Marce S, Balague O, Colomo L, et al. Lack of methylthioadenosine phosphorylase expression in mantle cell lymphoma is associated with shorter survival: implications for a potential targeted therapy. Clin Cancer Res. 2006;12(12):3754–61. doi: 10.1158/1078-0432.CCR-05-2780.
  62. Dreyling MH, Roulston D, Bohlander SK, et al. Codelition of CDKN2 and MTAP genes in a subset of non-Hodgkin’s lymphoma may be associated with histologic transformation from low-grade to diffuse large-cell lymphoma. Genes Chromos Cancer. 1998;22(1):72–8. doi: 10.1002/(sici)1098-2264(199805)22:1<72::aid-gcc10>3.3.co;2-g.
  63. Illei PB, Busch VW, Zakowski MF, Ladanyi M. Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas. Cancer Res. 2003;9(6):2108–13.
  64. Mora J, Alaminos M, de Torres C, et al. Comprehensive analysis of the 9p21 region in neuroblastoma suggests a role for genes mapping to 9p21–23 in the biology of favorable stage 4 tumours. Br J Cancer. 2004;91(6):1112–8. doi: 10.1038/sj.bjc.6602094.
  65. Hustinx SR, Hruban RH, Leoni LM, et al. Homozygous deletion of the MTAP gene in invasive adenocarcinoma of the pancreas and in periampullary cancer: a potential new target for therapy. Cancer Biol Ther. 2005;4(1):83–6. doi: 10.4161/cbt.4.1.1380.
  66. Hustinx SR, Leoni ML, Yeo CJ, et al. Concordant loss of MTAP and p16/CDRN2A expressions in pancreatic intraepithelial neoplasia: evidence of homozygous deletion in a noninvasive precursor lesion. Mod Pathol. 2005;18(7):959–63. doi: 10.1038/modpathol.3800377.
  67. Chen ZH, Zhang H, Savarese TM. Gene deletion chemoselectivity: codeletion of the genes for p16 (INK4), methylthioadenosine phosphorylase, and the alpha- and beta-interferons in human pancreatic cell carcinoma lines and its implications for. Cancer Res. 1996;56(5):1083–90.
  68. Brownhill SC, Taylor C, Burchill SA. Chromosome 9p21 gene copy number and prognostic significance of p16 in ESFT. Br J Cancer. 2007;96(12):1914–23. doi: 10.1038/sj.bjc.6603819.
  69. Conway C, Beswick S, Elliott F. Deletion at chromosome arm 9p in relation to BRAF and NRAS mutation and prognostic significance for primary melanoma. Genes Chromos Cancer. 2010;49(5):425–38. doi: 10.1002/gcc.20753.
  70. Worsham MJ, Chem KM, Tiwari N, et al. Fine-mapping loss of gene architecture at the CDKN2B (p15INK4b), CDKN2A (p14ARF, p16INK4a) and MTAP genes in head and neck squamous cell carcinoma. Arch Otol Head Neck Surg. 2006;132(4):409–15. doi: 10.1001/archotol.132.4.409.
  71. Mirebeau D, Acquaviva C, Suciu S, et al. The prognostic significance of CDKN2A, CDKN2B and EORTC studies 58881 and 58951. Haematologica. 2006;91(7):881–5.
  72. Tang B, Li YN, Kruger WD. Defects in methylthioadenosine phosphorylase is associated with but not responsible for methionine-dependent tumor cell growth. Cancer Res. 2000;60(19):5.
  73. Basu I, Locker J, Cassera MB, et al. Growth and metastases of human lung cancer are inhibited in mouse xenografts by a transition state analogue of 5ʹ-methilthioadenosine. J Biol Chem. 2010;286(6):4902–11. doi: 10.1074/jbc.M110.198374.
  74. Subhi AL, Diegelman P, Porter CW, et al. Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites. J Biol Chem. 2003;278(50):49868–73. doi: 10.1074/jbc.M308451200.
  75. Kenyon SH, Waterfield CJ, Timbrell JA, et al. Methionine synthase activity and sulphur amino acid levels in the rat liver tumor cells HTS and Phi-1. J. Biochem Pharmacol. 2002;63(3):381–91. doi: 10.1016/s0006-2952(01)00874-7.
  76. Ma E, Iwasaki M, Junko I, et al. Dietary intake of folate, vitamin B6, and vitamin B12, genetic polymorphism of related enzymes, and risk of breast cancer: a case-control study in Brazilian women. BMC Cancer. 2009;24(9):122. doi: 10.1186/1471-2407-9-122.
  77. Stern PH, Wallace CD, Hoffman RM. Altered methionine metabolism occurs in all members of a set of diverse human tumor cell lines. J Cell physiol. 1984;119(1):29–34. doi: 10.1002/jcp.1041190106.
  78. Lu M, Wang F, Qiu J. Methionine synthase A2756G polymorphism and breast cancer risk: a meta-analysis involving 18,953 subjects. Breast Cancer Res Treat. 2010;123(1):213–7. doi: 10.1007/s10549-010-0755-9.
  79. Linnebank M, Fliessbach K, Kolsch H, et al. The methionine synthase polymorphism c.2756Aright curved arrow G (D919G) is relevant for disease-free longevity. Int J Mol Med. 2005;16(4):759–61.
  80. Dhillon V, Thomas P, Fenech M. Effect of common polymorphisms in folate uptake and metabolism genes on frequency of micronucleated lymphocytes in a South Australian cohort. Mutat Res. 2009;665(1–2):1–6. doi: 10.1016/j.mrfmmm.2009.02.007.
  81. Beetstra S, Suthers G, Dhillon V, et al. Methionine-dependence phenotype in the de novo pathway in BRCA1 and BRCA2 mutation carriers with and without breast cancer. Cancer Epidemiol Biomark Prev. 2008;17(10):2565–71. doi: 10.1158/1055-9965.EPI-08-0140.
  82. Drennan CL, Huang S, Drummond J, et al. How a protein binds B12: A 3.0 A X-ray structure of B12-binding domains of methionine synthase. Science. 1994;266(5191):1669–74. doi: 10.1126/science.7992050.
  83. Tisdale MJ. Methionine metabolism in Walker carcinosarcoma in vitro. Eur J Cancer. 1980;16(3):407–14. doi: 10.1016/0014-2964(80)90360-6.
  84. Liteplo RG, Hipwell SE, Rosenblatt DS, et al. Changes in cobalamin metabolism are associated with the altered methionine auxotrophy of highly growth autonomous human melanoma. J Cell Physiol. 1991;149(2):332–8. doi: 10.1002/jcp.1041490222.
  85. Fiskerstrand T, Christensen B, Tysnes OB, et al. Development and reversion of methionine dependence in a human glioma cell line: relation to homocysteine remethylation and cobalamin status. Cancer Res. 1994;54(18):4899–906.
  86. Watkins D. Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines. Clin Invest Med. 1998;21(3):151–8.
  87. Tang B, Mustafa A, Gupta S, et al. Methionine-deficient diet induces post-transcriptional down-regulation of cystathionine beta-synthase. Nutrition. 2009;26(11–12):170–5. doi: 10.1016/j.nut.2009.10.006.
  88. Breillout F, Hadida F, Echinard-Garin P, et al. Decreased rat rhabdomyosarcoma pulmonary metastases in response to low methionine diet. Anticancer Res. 1987;7(4b):861–7.
  89. Komninou D, Leutzinger Y, Reddy BS, et al. Methionine restriction inhibits colon carcinogenesis. Nutr Cancer. 2006;54(2):202–8. doi: 10.1207/s15327914nc5402_6.
  90. Graziosi L, Mencarelli A, Renga B, et al. Epigenetic modulation by methionine deficiency attenuates the potential for gastric cancer cell dissemination. J Gastrointest Surg. 2013;17(1):39–49. doi: 10.1007/s11605-012-1996-1.
  91. Theuer RC. Effect of essential amino acid restriction on the growth of female C57BL mice and their implanted BW10232 adenocarcinomas. J Nutr. 1971;101(2):223–32.
  92. Caro P, Gomez J, Sanchez I, et al. Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuven Res. 2009;12(6):421–34. doi: 10.1089/rej.2009.0902.
  93. Ryu CS, Kwak HC, Lee KS, et al. Sulfur amino acid metabolism in doxorubicin-resistant breast cancer cells. Toxicol Appl Pharmacol. 2011;15;255(1):94–102. doi: 10.1016/j.taap.2011.06.004.
  94. Goseki N, Endo M. Thiol depletion and chemosensitization on nimustine hydrochloride by methionine-depleting total parenteral nutrition. Tohoku J Exp Med. 1990;161(3):227–39. doi: 10.1620/tjem.161.227.
  95. Hoshiya Y, Guo H, Kubota T, et al. Human tumors are methionine dependent in vivo. Anticancer Res. 1995;15(3):717–8.
  96. Epne DE, Morrow S, Wilcox M, Houghton JL. Nutrient intake and nutritional indexes in adults with metastatic cancer on a phase l clinical trial of dietary methionine restriction. Nutr Cancer. 2002;42(2):158–66. doi: 10.1207/S15327914NC422_2.
  97. Goseki N, Yamazaki S, Shimojyu K, et al. Synergistic effect of methionine-depleting total parenteral nutrition with 5-fluorouracil on human gastric cancer: a randomized, prospective clinical trial. Jpn J Cancer Res. 1995;86(5):484–9. doi: 10.1111/j.1349-7006.1995.tb03082.x.
  98. Durando X, Farges MC, Buc E, et al. Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: a feasibility study. Oncology. 2008;78(3–4):205–9. doi: 10.1159/000313700.
  99. Ornish D, Weidner G, Fair WR, et al. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol. 2005;174(3):1065–70. doi: 10.1097/01.ju.0000169487.49018.73.
  100. McCarty M, Barroso-Aranda J, Contreras F, et al. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med Hypotheses. 2009;72(2):125–8. doi: 10.1016/j.mehy.2008.07.044.
  101. Kack H, Sandmark J, Gibson K, et al. Crystal structure of diaminopelargonic acid synthase: evolutionary relationships between pyridoxal-5ʹ-phosphate-dependent enzymes. J Mol Biol. 1999;291:857–76. doi: 10.1006/jmbi.1999.2997.
  102. Fernandes HS, Silva Teixeira CS, Fernandes PA, et al. Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections. Expert Opin Ther Pat. 2017;27(3):283–97. doi: 10.1080/13543776.2017.1254194.
  103. Gay F, Aguera K, Senechal K, et al. Methionine tumor starvation by erythrocyte-encapsulated methionine gamma-lyase activity controlled with per os vitamin B6. Cancer Med. 2017. doi: 10.1002/cam4.1086.
  104. Покровский В.С., Трещалина Е.М. Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения. Клиническая онкогематология. 2014;7(1):28–38.
    [Pokrovskiy VS, Treshchalina YeM. Enzymes in oncohematology: relevant directions of experimental studies and prospects of clinical use. Klinicheskaya onkogematologiya. 2014;7(1):28–38. (In Russ)]
  105. Манухов И.В., Мамаева Д.В., Морозова Е.А. и др. L-метионин–гамма-лиаза Citrobacter freundii: клонирование гена и кинетические параметры фермента. Биохимия. 2006;71(4):454–63.
    [Manukhov IV, Mamaeva DV, Morozova EA, et al. L-methionine γ-lyase from Citrobacter freundii: cloning of the gene and kinetic parameters of the enzyme. Biokhimiya. 2006;71(4):454–63. (In Russ)]
  106. Cellarier E, Durando X, Vasson MP, et al. Methionine dependency and cancer treatment. Cancer Treat Rev. 2003;29(6):489–99. doi: 10.1016/s0305-7372(03)00118-x.
  107. Tan Y, Xu M, Hoffman RM. Broad selective efficacy of recombinant methioninase and polyethylene glycol-modified recombinant methioninase on cancer cells in vitro. Anticancer Res. 2010;30:1041–6.
  108. Kreis W, Hession C. Isolation and purification of L-methionine-alpha-deamino-gamma-mercaptomethane-lyase (L-methioninase) from Clostridium sporogenes. Cancer Res. 1973;33:1862–5.
  109. 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.
  110. El-Sayed SA, Shouman HM, Nassrat HM. Pharmacokinetics, immunogenicity and anticancer efficiency of Aspergillus flavipes L-methioninase. Enzyme Microb Technol. 2012;51(4):200–10. doi: 10.1016/j.enzmictec.2012.06.004.
  111. Huang K-Y, Hu H-Y, Tang Y-L, et al. High-level expression, purification and large-scale production of L-methionine γ-Lyase from Ideomarina as a novel anti-leucemic drug. Mar Drugs. 2015;13(8):5492–507. doi: 10.3390/md13085492.
  112. Yano S, Li S, Han Q, et al. Selective methioninase-inducted trap of cancer cells in S/G2 phase visualized by FUCCI imaging confers chemosensitivity. Oncotarget. 2014;5(18):8729–36. doi: 10.18632/oncotarget.2369.
  113. Nagahama T, Goseki N, Endo M. Doxorubicin and vincristine with methionine depletion contributed to survival in the Yoshida sarcoma bearing rats. Anticancer Res. 1998;18(1):25–31.
  114. Machrover D, Zittoun J, Broet Ph, et al. Cytotoxic synergism of methioninase in combination with 5-fluorouracil and folinic acid. Biochem Pharmacol. 2001;61(7):867–76. doi: 10.1016/s0006-2952(01)00560-3.
  115. Smiraglia DJ. Excessive CpG island hypermethylation in cancer cell lines versus primary human malignancies. Hum Mol Genet. 2001;10(13):1413–9. doi: 10.1093/hmg/10.13.1413.
  116. Jeanblanc M, Mousli M, Hopfner R, et al. The retinoblastoma gene and its product are targeted by ICBP90: a key mechanism in the G1/S transition during the cell cycle. Oncogene. 2005;24(49):7337–45. doi: 10.1038/sj.onc.1208878.
  117. Hu J, Cheung NK. Methionine depletion with recombinant methioninase: In vitro and in vivo efficacy against neuroblastoma and its synergism with chemotherapeutic drug. Int J Cancer. 2009;124(7):1700–6. doi: 10.1002/ijc.24104.
  118. Kokkinakis DM, Schold H, Hori H, et al. 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. doi: 10.1080/01635589709514624.
  119. Tan Y, Xu M, Guo H, et al. Anticancer efficacy of methioninase in vivo. Anticancer Res. 1996;16(6С):3931–6.
  120. 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.
  121. 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.
  122. Hoshiya Y, Kubota T, Matsuzaki SW, et al. Methionine starvation modulates the efficacy of cisplatin on human breast cancer in nude mice. Anticancer Res. 1996;16(6B):3515–7.
  123. Kokkinakis DM, Hoffman RM, Frenkel EP, et al. Synergy between methionine stress and chemotherapy in the treatment of brain tumor xenografts in athymic mice. Cancer Res. 2001;61(10):4017–23.
  124. Tan Y, Zavala JSr, Xu M, et al. Serum methionine depletion without side effects by methioninase in metastatic breast cancer patients. Anticancer Res. 1996;16(6):3937–42.
  125. Morozova EA, Anufrieva NV, Davydov DZ, et al. Plasma methionine depletion and pharmacokinetic properties in mice of methionine γ-lyase from Citrobacter freundii, Clostridium tetani and Clostridium sporogenes. Biomed Pharmacother. 2017;88:978–84. doi: 10.1016/j.biopha.2017.01.127.
  126. Покровский В.С., Лесная Н.А., Трещалина Е.М. и др. Перспективы разработки новых ферментных противоопухолевых препаратов. Вопросы онкологии. 2011;57(2):155–64.
    [Pokrovskii VS, Lesnaya NA, Treshchalina EM, et al. Perspectives in the development of new enzyme anticancer treatments. Voprosy onkologii. 2011;57(2):155–64. (In Russ)]
  127. Покровская М.В., Покровский В.С., Соколов Н.Н. Дифференциальная среда для выявления штаммов бактерий-продуцентов L-аспарагиназ. Прикладная биохимия и микробиология. 2011;47(2):183–6.
    [Pokrovskaya MV, Pokrovskii VS, Sokolov NN, et al. Differential medium for revealing bacterial producer strains of L-asparaginases.) Prikladnaya biokhimiya i mikrobiologiya. 2011;47(2):183–6. (In Russ)]
  128. Pokrovskii VS, Pokrovskaya MV, Aleksandrova SS, et al. Physicochemical properties and antiproliferative activity of recombinant Yersinia pseudotuberculosis L-asparaginase. Appl Biochem Microbiol. 2013;49(1):18–22. doi: 10.1134/s000368381301016x.
  129. Pokrovskaya MV, Pokrovskiy VS, Aleksandrova SS, et al. Recombinant intracellular Rhodospirillum rubrum L-asparaginase with low L-glutaminase activity and antiproliferative effect. Biochem (Moscow) Suppl. Series B: Biomed Chem. 2012;6(2):123–31. doi: 10.1134/s1990750812020096.
  130. Sidoruk KV, Bogush VG, Pokrovsky VS, et al. Creation of a producent, optimization of expression, and purification of recombinant Yersinia pseudotuberculosis L-asparaginase. Bull Exp Biol Med. 2011;152(2):219–23. doi: 10.1007/s10517-011-1493-7.
  131. Pokrovsky VS, Pokrovskaya MV, Aleksandrova SS, et al. Comparative immunogenicity and structural analysis of epitopes of different bacterial L-asparaginases. BMC Cancer. 2016;16(1):89. doi: 10.1186/s12885-016-2125-4.
  132. Sannikova EP, Bulushova NV, Cheperegin SE, et al. The modified heparin-binding L-asparaginase of Wolinella succinogenes. Mol Biotechnol. 2016;58(8–9):528–39. doi: 10.1007/s12033-016-9950-1.
  133. Pokrovskaya MV, Aleksandrova SS, Pokrovsky VS, et al. Identification of functional regions in the Rhodospirillum rubrum L-asparaginase by site-directed mutagenesis. Mol Biotechnol. 2015;57(3):251–64. doi: 10.1007/s12033-014-9819-0.
  134. Покровский В.С., Лукашева Е.В., Трещалина Е.М. и др. Экспериментальная оценка синергизма цисплатина с L-лизин-α-оксидазой. Вопросы онкологии. 2014;60(1):90–3.
    [Pokrovskii VS, Lukasheva EV, Treshchalina EM, et al. Experimental evaluation of synergism of cisplatin with L-lysine-α-oxidase.) Voprosy onkologii. 2014;60(1):90–3. (In Russ)]
  135. Покровский В.С., Трещалина Е.М., Трещалин И.Д. и др. Оценка противоопухолевой эффективности комбинации L-лизин-α-оксидазы и иринотекана в эксперименте. Онкология. 2012;2:58–61.
    [Pokrovskii VS, Treshchalina EM, Treshchalin ID, et al. Evaluation of the antitumor efficacy of a combination of L-lysine α-oxidase and irinotecan in the experiment. Onkologiya. 2012;2:58–61. (In Russ)]

 

 

Chromothripsis in Oncology: Literature Review and Case Report

MYELOID TUMORS , , ,

NN Mamaev1, TL Gindina1, EG Boichenko2

1 RM Gorbacheva Scientific Research Institute of Pediatric Hematology and Transplantation; Pavlov First Saint Petersburg State Medical University, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022

2 Municipal Children’s Hospital No. 1, 14 Avangardnaya str., Saint Petersburg, Russian Federation, 198205

For correspondence: Tat’yana Leonidovna Gindina, PhD, 6/8 L’va Tolstogo str., Saint Petersburg, Russian Federation, 197022; Tel: +7(812)233-12-43; e-mail: cytogenetics.bmt.lab@gmail.com

For citation: Mamaev NN, Gindina TL, Boichenko EG. Chromothripsis in Oncology: Literature Review and Case Report. Clinical oncohematology. 2017;10(2):191–205 (In Russ).

DOI: 10.21320/2500-2139-2017-10-2-191-205

ABSTRACT

The article presents a clinical case and literature review dwelling on the recently discovered chromothripsis phenomenon in oncology. Chromothripsis is a type of complex genome changes when a chromosome is first torn into dozens and even thousands of fragments, and then these fragments are bound in a random manner. Sometimes, several chromosomes are involved in the restructuring. As a result, genome mutant zones are formed which trigger malignancies and congenital diseases. In other words, the use of certain methodological approaches (multicolor fluorescence in situ hybridization, SKY technique, and some others) permits to observe under a microscope the splitting of two or more chromosomes and further reunification of these fragments into new unusual two- or multicolor structures, chromosomal markers. Chromothripsis is a rare phenomenon with a peculiar pattern observed in clones of cells of various tumors including hematopoietic and lymphoid tissue malignancies. There are published data on a higher incidence of this phenomenon in patients with myelodysplastic syndromes and bone tumors. TP53 gene mutations play an important role in the development of chromothripsis. The use of paired-sequencing DNA or SNP approaches in oncology is promising both in theoretical and clinical application. The first subject cohort should include patients with TP53 and MLL gene mutations, complex chromosomal aberrations, EVI-1 gene overexpression, and some others. The article presents the chromothripsis phenomenon in an 8-month-old girl with M7 acute myeloid leukemia.

Keywords: chromothripsis, oncohematology, cancer, TP53 gene mutations.

Received: October 2, 2016

Accepted: January 6, 2017

Read in PDF (RUS)pdficon

REFERENCES

  1. Stephens PJ, Greenman CD, Fu B, et al. Massive genomic rearrangement acquired in a single catastrophic event during cancer development. Cell. 2011;144(1):27–40. doi: 10.1016/j.cell.2010.11.055.
  2. Righolt C, Mai S. Shattered and stitched chromosomes – chromothripsis and chromoanasynthesis – manifestation of a new chromosome crisis. Genes Chromos Cancer. 2012;51(11):975–81. doi: 10.1002/gcc.21981.
  3. Tan L, Xu L-H, et al. Small Lymphocytic Lymphoma/Chronic lymphocytic leukemia with chromothripsis in an old woman. Chin Med J. 2015;128(7):985–7. doi: 10.4103/0366-6999.154329.
  4. de Pagter MS, Kloosterman WP. The diverse effects of complex chromosome rearrangements and chromothripsis in cancer development. In: BM Ghadimi, T Ried, eds. Chromosomal Instability in Cancer Cells. Recent Results in Cancer Research 200. Switzerland: Springer International Publishing; 2015. рр. 165–93. doi: 10.1007/978-3-319-20291-4_8.
  5. Magrangeas F, Avet-Loiseau H, Munshi NC, et al. Chromothripsis identifies a rare and aggressive entity among newly diagnosed multiple myeloma patients. Blood. 2011;118(3):675–8. doi: 10.1182/blood-2011-03-344069.
  6. Pei J, Jhanwar SC, Testa J R. Chromothripsis in a case of TP53-deficient chronic lymphocytic leukemia. Leuk Res Rep. 2012;1(1):4–6. doi: 10.1016/j.lrr.2012.09.001.
  7. Rausch T, Jones DT, Zapatka M, et al. Genome sequencing of pediatric medulloblastoma links catastrophic DNA rearrangements with TP53 mutations. Cell. 2012;148(1–2):59–71. doi: 10.101.1016/j.cell.2011.12.013.
  8. Ortega V, Chaubey A, Mendiola C, et al. Complex chromosome rearrangements in B-cell lymphoma: Evidence of chromoanagenesis? A case report. Neoplasia. 2016;18(4):223–8. doi: 10.1016/j.neo.2016.02.004.
  9. Govind SK, Zia A, Hennings-Yeomans PH, et al. ShatterProof: operational detection and quantification of chromothripsis. BMC Bioinform. 2014;15(1):78. doi: 10.1186/1471-2105-15-78.
  10. Korbel JO, Campbell PJ. Criteria for inference of chromothripsis in cancer genomes. Cell. 2013;152(6):1226–36. doi: 10.1016/j.cell.2013.02.023.
  11. Baca SC, Prandi D, Lawrence MS, et al. Punctuated evolution of prostate cancer genomes. Cell. 2013;153(3):666–77. doi: 10.1016/j.cell.2013.03.021.
  12. Kloosterman WP, Koster J, Molenaar JJ. Prevalence and clinical implications of chromothripsis in cancer genomes. Curr Opin Oncol. 2014;26(1):64–72. doi: 10.1097/CCO.0000000000000038.
  13. Nones K, Waddell N, Wayte N, et al. Genomic catastrophes frequently arise in esophageal adenocarcinoma and drive tumorigenesis. Nat Commun. 2014;5:5224. doi: 10.1038/ncomms6224.
  14. Maher CA, Wilson RK. Chromothripsis and human disease: piecing together the shattering process. Cell. 2012;148(1–2):29–32. doi: 10.1016/j.cell.2012.01.006.
  15. Alves TI, Hiltemann S, Hartjes T, et al. Gene fusions by chromothripsis of chromosome 5q in the VCaP prostate cancer cell line. Hum Genet. 2013;132:709–13. doi: 10.1007/s00439-013-1308-1.
  16. Nagel S, Mever C, Quantmeier H, et al. Chromothripsis in Hodgkin lymphoma. Genes Chromos Cancer. 2013;52(8):791–7. doi: 10.1002/gcc.22069.
  17. Salaverria I, Martın-Garcia D, Lopez C, et al. Detection of chromothripsis-like patterns with a custom array platform for chronic lymphocytic leukemia. Genes Chromos Cancer. 2015;54(11):668–80. doi: 10.1002/gcc.22277.
  18. Li Y, Schwaab C, Ryan SL, et al. Constitutional somatic rearrangement of chromosome 21 in acute lymphoblastic leukemia. Nature. 2014;508(7494):98–102. doi: 10.1038/nature13115.
  19. de Pagter MS, van Roosmalen MJ, Baas AF, et al. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet. 2015;96(4):651–6. doi: 10.1016/j.ajhg.2015.02.005.
  20. Bignell GR, Greenman CD, Davies H, et al. Signatures of mutation and selection in the cancer genome. Nature. 2010;463(7283):893–8. doi: 10.1038/nature08768.
  21. Adhvaryu SG, Vyas RC, Jani KH, et al. Complex translocation involving chromosomes #1, #9, and #22 in a patient with chronic myelogenous leukemia. Cancer Genet Cytogenet. 1988;32(2):277–80. doi: 10.1016/0165-4608(88)90291-9.
  22. Kadam PR, Nanjangud GJ, Advani SH. The occurrence of variant Ph translocations in chronic myeloid leukemia (CML): a report of six cases. Hematol Oncol. 1990;8(6):303–12. doi: 10.1002/hon.2900080602.
  23. Fitzgerald PH, Morris CM. Complex chromosomal translocations in the Philadelphia chromosome leukemias. Serial translocations or a concerted genomic rearrangement. Cancer Genet Cytogenet. 1991;57(2):143–51. doi: 10.1016/0165-4608(91)90145-k.
  24. Nishi Y, Akiyama K, Korf BR. Characterization of N-myc amplification in a human neuroblastoma cell line by clones isolated following the phenol emulsion reassociation technique and by hexagonal field gel electrophoresis. Mamm Genome. 1992;2(1):11–20. doi: 10.1007/bf00570436.
  25. Cowell JK. Double minutes and homogenously staining regions: gene amplification in mammalian cells. Annu Rev Genet. 1982;16(1):21–59. doi: 10.1146/annurev.ge.16.120182.000321.
  26. Cowell JK, Miller OJ. Occurrence and evolution of homogenously staining regions may be due to breakage-fusion-bridge cycles following telomere loss. Chromosoma. 1983;88(3):2016–21. doi: 10.1007/bf00285623.
  27. Shimizu N, Shindaki K, Kaneko-Sasaguri Y, et al. When, where and how the bridge breaks: anaphase bridge breakage plays a crucial role in gene amplification and HSR generation. Exp Cell Res. 2005;302(2):233–43. doi: 10.1016/j.yexcr.2004.09.001.
  28. Shimizu N. Extra chromosomal double minutes and chromosomal homogenously staining regions as probes for chromosome research. Cytogenet Genome Res. 2009;124(3–4):312–26. doi: 10.1159/000218135.
  29. Bignell GR, Santarius Th, Pole JCM, et al. Architectures of somatic genomic rearrangement in human cancer amplicons at sequence-level resolution. Genome Res. 2007;17(9):1296–303. doi: 10.1101/gr.6522707.
  30. Crasta K, Ganem NJ, Dagher R, et al. DNA breaks and chromosome pulverization from errors in mitosis. Nature. 2012;482(7383):53–8. doi: 10.1038/nature10802.
  31. Bassaganyas L, Bea S, Escaramı G, et al. Sporadic and reversible chromothripsis in chronic lymphocytic leukemia revealed by longitudinal genomic analysis. Leukemia. 2013;27(12):2376–9. doi: 10.1038/leu.2013.127.
  32. Zehentner BK, Hartmann L, Johnson KRT, et al. Array-based karyotyping in plasma cell neoplasia after plasma cell enrichment increases detection of genomic aberrations. Am J Clin Pathol. 2012;138(4):579–89. doi: 10.1309/ajcpkw31baimvgst.
  33. Jacoby MA, de Jesus Pizarro R, Shao J, et al. The DNA double-strand break response is abnormal in myeloblasts from patients with therapy-related acute myeloid leukemia. Leukemia. 2014;28(6):1242–51. doi: 10.1038/leu.2013.368.
  34. Zemanova Z, Michalova K, Buryova H, et al. Involvement of deleted chromosome 5 in complex chromosomal aberrations in newly diagnosed myelodysplastic syndromes (MDS) is correlated with extremely adverse prognosis. Leukemia Res. 2014;38(5):537–44. doi: 10.1016/j.leukres.2014.01.012.
  35. Agrawal A, Modi A, Alagusundaramoorthy SS, et al. Chromothripsis: Basis of a concurrent unusual association between myelodysplastic syndrome and primary ciliary dyskinesia. Case Rep Hematol. 2014:1–5. doi. 10.1155/2014/149878.
  36. Forment JV, Kaidi A, Jackson SP. Chromothripsis and cancer: causes, and consequences of chromosome shattering. Nat Rev Cancer. 2012;12(10):663–70. doi: 10.1038/nrc3352.
  37. Zhang CZ. Chromothripsis from DNA damage in micronuclei. Nature. 2015;522(7555):179–84. doi: 10.1038/nature14493.
  38. Kim TM, Ruibin Xi, Lovelace J, et al. Functional genomic analysis of chromosomal aberrations in a compendium of 8000 cancer genomes. Genome Res. 2013;23(2):217–27. doi: 10.1101/gr.140301.112.
  39. Malhotra A, Lindberg M, Faust GG, et al. Breakpoint profiling of 84 cancer genomes reveals numerous complex rearrangements spawned by homology-independent mechanisms. Genome Res. 2013;23(5):762–76. doi: 10.1101/gr.143677.112.
  40. Yang L, Luquette LJ, Gehlenborg N, et al. Diverse mechanisms of somatic structural variations in human cancer genomes. Cell. 2013;53(4):919–29. doi: 10.1016/j.cell.2013.04.010.
  41. Zack T, Luquette LJ, Gehlenborg N, et al. Pan-cancer patterns of somatic copy number alteration. Nat Genet. 2013;45(10):1134–40. doi: 10.1016/j.cell.2013.04.010.
  42. Cai H, Kumar N, Bagheri HC, et al. Chromothripsis-like patterns are recurring but heterogeneously distributed features in a survey of 22,347 cancer genome screens. BMC Genomics. 2014;15(1):82–95. doi: 10.1186/1471-2164-15-82.
  43. Przybytkowski E, Lenkiewicz E, Barrett MT, et al. Chromosome-breakage genomic instability and chromothripsis in breast cancer. BMC Genomics. 2014;15(1):579. doi: 10.1186/1471-2164-15-579.
  44. Kovtun IV, Murphy SJ, Johnson SH, et al. Chromosomal catastrophe is a frequent event in clinically insignificant prostate cancer. Oncotarget. 2015;6(30):29087–96. doi: 10.18632/oncotarget.4900.
  45. Morrison CD, Liu P, Woloszynska-Read A, et al. Whole-genome sequencing identifies genomic heterogeneity at a nucleotide and chromosomal level in bladder cancer. Proc Natl Acad Sci USA. 2014;111(6):E672–81. doi: 10.1073/pnas.1313580111.
  46. Fukuoka K, Fukushima S, Yamashita S, et al. Molecular classification of ependymomas in a Japanese cohort. Neuro-Oncology. 2015;17(Suppl 3):iii6. doi: 10.1093/neuonc/nov061.21.
  47. Jones DT, Jager N, Kool M, et al. Dissecting the genomic complexity underlying medulloblastoma. Nature. 2012;488(7409):100–5. doi: 10.1038/nature11284.
  48. Kool M, Jones DT, Jager N, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014;25(3):393–405. doi: 10.1016/j.ccr.2014.02.004.
  49. Bayani J, Zielenska M, Pandita A, et al. Spectral karyotyping identifies recurrent complex rearrangements of chromosomes 8, 17, and 20 in osteosarcomas. Genes Chromos Cancer. 2003;36(1):7–16. doi: 10.1002/gcc.10132.
  50. Ivkov R, Bunz F. Pathways to chromothripsis. Cell Cycle. 2015;14(18):2886–90. doi: 10.1080/15384101.2015.1068483.
  51. Northcott PA, Shih DJH, Peacock J, et al. Subgroup-specific structural variation across 1,000 medulloblastoma genomes. Nature. 2012;488(7409):49–56. doi: 10.1038/nature11327.
  52. Cohen A, Sato M, Aldape K, et al. DNA copy number analysis of Grade II-III and Grade IV gliomas reveals differences in molecular ontogeny including chromothripsis associated with IDH mutation status. Acta Neuropathol Commun. 2015;3(1):34. doi: 10.1186/s40478-015-0213-3.
  53. Furgason JM, Koncar RF, Sharon K, et al. Whole genome sequence analysis links chromothripsis to EGFR, MDM2, MDM4, and CDK4 amplification in glioblastoma. Oncoscience. 2015;2(7):618–28. doi: 10.18632/oncoscience.178.
  54. Molenaar JJ, Koster J, Zwijnenburg DA, et al Sequencing of neuroblastoma identifies chromothripsis and defects in neuritogenesis genes. Nature. 2012;483(7391):589–93. doi: 10.1038/nature10910.
  55. Peifer M, Hertwig F, Roels F, et al. Telomerase activation by genomic rearrangements in high-risk neuroblastoma. Nature. 2015;526(7575):700–4. doi: 10.1038/nature14980.
  56. Natrajan R, Mackay A, Lambros MB, et al. A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers. J Pathol. 2012;227(1):29–41. doi: 10.1002/path.4003.
  57. Nik-Zeinal B, Alexandrov LB, Wedge DC, et al. Mutational processes molding the genomes of 21 breast cancers. Cell. 2012;149(6):979–93. doi: 10.1016/j.cell.2012.04.024.
  58. Tang M-H, Dahlgren M, Brueffer C, et al. Remarkable similarities of chromosomal rearrangements between primary human breast cancers and matched distant metastases as revealed by whole-genome sequencing. Oncotarget. 2015;6(35):37169–84. doi: 10.18632/oncotarget.5951.
  59. Wu C, Wyatt AW, McPherson A, et al. Polygene fusion transcripts and chromothripsis in prostate cancer. Genes Chromos Cancer. 2012;51(12):1144–53. doi: 10.1002/gcc.21999.
  60. George J, Lim JS, Jang SJ, et al. Comprehensive genomic profiles of small cell lung cancer. Nature. 2015;524(7563):47–53. doi: 10.1038/nature14664.
  61. Govindan R, Ding L, Griffith M, et al. Genomic landscape of Non-small cell lung cancer in smokers and never-smokers. Cell. 2012;150(6):1121–34. doi: 10.1016/j.cell.2012.08.024.
  62. Campbell PJ, Yachida S, Mudie, et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature. 2010;467(7319):1109–13. doi: 10.1038/nature09460.
  63. Kloosterman WP, Hoogstraat M, Paling O, et al. Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer. Genome Biol. 2011;12(10):R103. doi: 10.1186/gb-2011-12-10-r103.
  64. Jiang Z, Jhunjhunwala S, Liu J, et al. The effects of hepatitis B virus integration inti the genomes of hepatocellular carcinoma patients. Genome Res. 2012;22(4):593–601. doi: 10.1101/gr.133926.111.
  65. McEvoy J, Nagahawatte P, Finkelstein D, et al. RB1 gene inactivation by chromothripsis in human retinoblastoma. Oncotarget. 2014;5(2):438–50. doi: 10.18632/oncotarget.1686.
  66. Kloosterman WP, Guryev V, van Roosmalen M, et al. Chromothripsis as a mechanism driving complex de novo structural rearrangements in the germline. Hum Mol Genet. 2011;20(10):1916–24. doi: 10.1093/hmg/ddr073.
  67. Chiang C, Jacobsen JC, Ernst C, et al. Complex reorganization and predominant non-homologous repair following chromosomal breakage in karyotypically balanced germline rearrangements and transgenic integration. Nat Genet. 2012;44(4):390–7. doi: 10.1038/ng.2202.
  68. Madan K. Balanced complex chromosome rearrangements: reproductive aspects. A review. Am J Med Genet. 2012;158A(4):947–63. doi: 10.1002/ajmg.a.35220.
  69. Pellestor F. Chromothripsis: how does such a catastrophic event impact human reproduction? Hum Reprod. 2014;29(3):388–93. doi: 10.1093/humrep/deu003.
  70. Weckselblatt B, Hermetz KE, Rudd MK. Unbalanced translocations arise from diverse mutational mechanisms including chromothripsis. Genome Res. 2015;25(7):937–47. doi: 10.1101/gr.191247.115.
  71. Macera MJ, Sobrino A, Levy B, et al. Prenatal diagnosis of chromothripsis, with nine breaks characterized by karyotyping, FISH, microarray and whole-genome sequencing. Prenat Diagn. 2015;35(3):299–301. doi: 10.1002/pd.4456.
  72. de Pagter MS, van Roosmalen MJ, Baas AF, et al. Chromothripsis in healthy individuals affects multiple protein-coding genes and can result in severe congenital abnormalities in offspring. Am J Hum Genet. 2015;96(4):651–6. doi: 10.1016/j.ajhg.2015.02.005.
  73. Kloosterman WP, Cuppen E. Chromothripsis in congenital disorders and cancer: similarities and differences. Curr Opin Cell Biol. 2013;25(3):341–8. doi: 10.1016/j.ceb.2013.02.008.
  74. Poot M, Haaf T. Mechanisms of origin, phenotypic effects and diagnostic implications of complex chromosome rearrangements. Mol Syndromol. 2015;6(3):110–34. doi: 10.1159/000438812.
  75. Liu P, Erez A, Nagamani SCS, et al. Chromosome catastrophes involve replication mechanisms generating complex genomic rearrangements. Cell. 2011;146(6):889–903. doi: 10.1016/j.cell.2011.07.042.
  76. Kloosterman WP, Tavakoli-Yaraki M, van Roosmalen MJ, et al. Constitutional chromothripsis rearrangements involve clustered double-stranded DNA breaks and nonhomologous repair mechanisms. Cell Rep. 2012;1(6):648–55. doi: 10.1016/j.celrep.2012.05.009.
  77. Hatch EM, Fischer AH, Deerinck ThJ, Hetzer MW. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell. 2013;154(1):47–60. doi: 10.1016/j.cell.2013.06.007.
  78. Zhang CZ, Leibowitz ML, Pellman D. Chromothripsis and beyond: rapid genome evolution from complex chromosomal rearrangements. Genes Dev. 2013;27(23):2513–30. doi: 10.1101/gad.229559.113.
  79. Morishita M, Muramatsu T, Suto Y, et al. Chromothripsis-like chromosomal rearrangements induced by ionizing radiation using proton microbeam irradiation system. Oncotarget. 2015;7(9):10182–92. doi: 10.18632/oncotarget.7186.
  80. Holland AJ, Cleveland DW. Mechanisms and consequences of localized, complex chromosomal rearrangements in cancer and developmental diseases. Nat Med. 2012;18(11):1630–8. doi: 10.1038/nm.2988.
  81. Sorzano CO, Pascual-Montano A, Sanchez de Diego A, et al. Chromothripsis: breakage-fusion-bridge over and over again. Cell Cycle. 2013;12(13):2016–23. doi: 10.4161/cc.25266.
  82. Mardin BR, Drainas AP, Waszak SM, et al. A cell-based model system links chromothripsis with hyperploidy. Mol System Biol. 2015;11(9):828–41. doi: 10.15252/msb.20156505.
  83. Zainuddin N, Murray F, Kanduri M, et al. TP53 mutations are infrequent in newly diagnosed chronic lymphocytic leukemia. Leuk Res. 2011;35(2):272–4. doi: 10.1016/j.leukres.2010.08.023.
  84. Мамаев Н.Н., Горбунова А.В., Гиндина Т.Л. и др. Лейкозы и миелодиспластические синдромы с высокой экспрессией гена EVI1: теоретические и клинические аспекты. Клиническая онкогематология. 2012;5(4):361–4.
    [Mamaev NN, Gorbunova AV, Gindina TL, et al. Leukemias and myelodysplastic syndromes with high expression of EVI1: theoretical and clinical aspects. Klinicheskaya onkogematologiya. 2012;5(4):361–4. (In Russ)]
  85. Гиндина Т.Л., Мамаев Н.Н., Бархатов И.М. и др. Сложные повреждения хромосом у больных с рецидивами острых лейкозов после аллогенной трансплантации гемопоэтических стволовых клеток. Терапевтический архив. 2012;8:61–6.
    [Gindina TL, Mamaev NN, Barkhatov IM, et al. Complex chromosome damages in patients with recurrent acute leukemias after allogeneic hematopoietic stem cell transplantations. Terapevticheskii arkhiv. 2012;8:61–6. (In Russ)]
  86. Гиндина Т.Л., Мамаев Н.Н., Николаева Е.Н. и др. Анализ хромосомных нарушений у детей и подростков с посттрансплантационными рецидивами острых лейкозов. Клиническая онкогематология. 2015;8(4):420–7. doi: 10.21320/2500-2139-2015-8-4-420-427.
    [Gindina TL, Mamaev NN, Nikolaeva EN, et al. Analysis of Karyotype Aberrations in Children and Adolescents with Post-Transplantation Relapses of Acute Leukemia. Clinical oncohematology. 2015;8(4):420–7. doi: 10.21320/2500-2139-2015-8-4-420-427. (In Russ)]
  87. MacKinnon, Campbell. Cancer Genet. 2013;206:238–51.

Anemias in Oncology: Potential of Maintenance Therapy

MAINTENANCE THERAPY , , , ,

AV Snegovoi, VB Larionova, LV Manzyuk, IB Kononenko

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Anton Vladimirovich Snegovoi, PhD, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-41-09; e-mail: anvs2012@gmail.com

For citation: Snegovoi AV, Larionova VB, Manzyuk LV, Kononenko IB. Anemias in Oncology: Potential of Maintenance Therapy. Clinical oncohematology. 2016;9(3):326-35 (In Russ).

DOI: 10.21320/2500-2139-2016-9-3-326-35

ABSTRACT

Development of anemia during chemotherapy or chemoradiotherapy of malignancies is a serious adverse event negatively affecting the quality of life and effectiveness of the treatment. In this regard, the leading consensus committees of NCCN, ESMO, ASCO, and RUSSCO have prepared and are regularly updating recommendations for diagnosing and treatment of anemia in cancer patients. The article presents recent data on the pathogenesis and methods of treatment of anemia in cancer patients, including administration of erythropoiesis stimulating agents: recombinant erythropoietins, intravenous iron products, vitamins, and red blood cell transfusions.

Keywords: cancer, anemia, erythropoietins, intravenous iron products, red blood cell transfusions.

Received: February 29, 2016

Accepted: March 31, 2016

Read in PDF(RUS)pdficon

REFERENCES

  1. Knight K, Wade S, Balducci L. Prevalence and outcome of anemia in cancer: a systematic review of the literature. Am J Med. 2004;116(7);11–26. doi: 10.1016/j.amjmed.2003.12.008.
  2. Schrijvers D, De Samblanx H, Roila F. Erythropoiesis-stimulating agents in the treatment of anaemia in cancer patients: ESMO Clinical Practice Guidelines for use. Ann Oncol. 2010;21(Suppl 5):v244–v247. doi: 10.1093/annonc/mdq202.
  3. Ludwig H, Van Belle S, Barrett-Lee P, et al. The European Cancer Anaemia Survey (ECAS): A large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur J Cancer. 2004;40(15):2293–306. doi: 10.1016/j.ejca.2004.06.019.
  4. Groopman J, Itri L. Chemotherapy-induced anemia in adults: incidence and treatment. J Nat Cancer Inst. 1999;91(19):1616–34. doi: 10.1093/jnci/91.19.1616.
  5. Food and Drug Administration. Jevtana (cabazitaxel) Injection Label Information. [Internet] Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/201023lbl.pdf. (accessed 12.11.2015).
  6. Food and Drug Administration. Taxotere (docetaxel) Injection Label Information. [Internet] Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020449s059lbl.pdf (accessed 12.11.2015).
  7. Food and Drug Administration. Xtandi (enzalutamide) Capsules Label Information. [Internet] Available from: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/203415lbl.pdf. (accessed 12.11.2015).
  8. Cella D. Quality of life and clinical decisions in chemotherapy-induced anemia. Oncology (Williston Park). 2006;20(8 Suppl 6):25–8.
  9. Caro JJ, Salas M, Ward A, et al. Anemia as an independent prognostic factor for survival in patients with cancer: a systemic, quantitative review. Cancer. 2001;91(12):2214–21. doi: 10.1002/1097-0142(20010615)91:12<2214::aid-cncr1251>3.0.co;2-p.
  10. Glaspy J. Update on Safety of ESAs in Cancer-Induced Anemia. J Natl Compr Cancer Network. 2012;10(5):659–66.
  11. Nowrousian M, Smyth JF, et al, eds. rhErythropoietin in cancer supportive treatment. New York: Marcel Dekker Inc; 1996. pp. 13–34.
  12. Павлов А.Д., Морщакова Е.Ф., Румянцев А.Г. Эритропоэз, эритропоэтин, железо. Молекулярные и клинические аспекты. М.: ГЭОТАР-Медиа, 2011. 304 с.
    [Pavlov AD, Morshchakova EF, Rumyantsev AG. Eritropoez, eritropoetin, zhelezo. Molekulyarnye i klinicheskie aspekty. (Erythropoiesis, erythropoietin, and iron. Molecular and clinical aspects.) Moscow: GEOTAR-Media Publ.; 2011. 304 p. (In Russ)]
  13. Grotto HZ. Anaemia of cancer: an overview of mechanisms involved in its pathogenesis. Med Oncol. 2008;25(1):12–21. doi: 10.1007/s12032-007-9000-8.
  14. Aapro M, Osterborg A, Gascon P, et al. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron. Ann Oncol. 2012;23(8):1954–62. doi: 10.1093/annonc/mds112.
  15. Khorana AA, Francis CW, Blumberg N, et al. Blood transfusions, thrombosis and mortality in hospitalized cancer patients. Arch Int Med. 2008;168(21):2377–81. doi: 10.1001/archinte.168.21.2377.
  16. Amato A, Pescatori M. Perioperative blood transfusions for the recurrence of colorectal cancer. Cochrane database syst.rev. 2006;25(1):CD005033. doi: 10.1002/14651858.cd005033.pub2.
  17. Hoff CM, Lassen P, Eriksen JG, et al. Does transfusion improve the outcome for HNSCC patients treated with radiotherapy? Results from the randomized DAHANCA 5 and 7 trials. Acta Oncologica. 2011;50(7):1006–14. doi: 10.3109/0284186X.2011.592650.
  18. Egrie JC, Browne JK. Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer. 2001;84(Suppl 1):3–10. doi: 10.1054/bjoc.2001.1746.
  19. Bohlius J, Wilson J, Seidenfeld J, et al. Recombinant human erythropoietins and cancer patients: updated meta-analysis of 57 studies including 9353 patients. J Natl Cancer Inst. 2006;98(10):708–14. doi: 10.1093/jnci/djj189.
  20. Tonelli M, Hemmelgarn B, Reiman T, et al. Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis. CMAJ. 2009;180(11):E62–E71. doi: 10.1503/cmaj.090470.
  21. Bennett C, Silver S, Djulbegovic B, et al. Venous thromboembolism and mortality associated with recombinant erythropoietin and darbepoetin administration for the treatment of cancer-associated anemia. JAMA. 2008;299(8):914–24. doi: 10.1001/jama.299.8.914.
  22. Ludwig H, Crawford J, Osterborg A, et al. Pooled analysis of individual patient-level data from all randomized, double-blind, placebo-controlled trials of darbepoetin alfa in the treatment of patients with chemotherapy-induced anemia. J Clin Oncol. 2009;27(17):2838–47. doi: 10.1200/jco.2008.19.1130.
  23. Glaspy J, Crawford J, Vansteenkiste J, et al. Erythropoiesis-stimulating agents in oncology: a study-level meta-analysis of survival and other safety outcomes. Br J Cancer. 2010;102(2):301–15. doi: 10.1038/sj.bjc.6605498.
  24. Oncologic Drug Advisory Committee (ODAC) Meeting Information Package. Darbepoetin alfa (BLA #103951) and Epoetin alfa (BLA #103234). [Internet] Available from: http://www.scribd.com/doc/1117102/US-Food-and-Drug-Administration-20074301b20101Amgen. (accessed 20.02.2016).
  25. Glaspy J, Osterborg A, Ludwig H, et al. Evaluation of the association between (Hb) events and safety outcomes in cancer patients with chemotherapy induced anemia: an integrated analysis of patient-level data from 6 randomized, placebo-controlled trials of darbepoetin. Eur J Cancer. 2007;5(4):147–8. doi: 10.1016/s1359-6349(07)70639-0.
  26. Снеговой А.В., Aapro M., Давиденко И.С. и др. Практические рекомендации по лечению анемии у онкологических больных. Злокачественные опухоли. 2015;4:316–26. doi: 10.18027/2224-5057-2015-4s-316-326. [Snegovoi AV, Aapro M, Davidenko IS, et al. Practical recommendations for management of anemia in cancer patients. Zlokachestvennye opukholi. 2015;4:316–26. doi: 10.18027/2224-5057-2015-4s-316-326. (In Russ)]
  27. Henke M, Laszig R, Rube C, et al. Erythropoietin to treat head and neck cancer patients with anaemia undergoing radiotherapy: randomised, double-blind, placebo-controlled trial. The Lancet. 2003;362(9392):1255–60. doi: 10.1016/s0140-6736(03)14567-9.
  28. Leyland-Jones B, Semiglazov V, Pawlicki M, et al. Maintaining normal hemoglobin levels with epoetin alfa in mainly nonanemic patients with metastatic breast cancer receiving first-line chemotherapy: a survival study. J Clin Oncol. 2005;23(25):5960–72. doi: 10.1200/jco.2005.06.150.
  29. Delarue R, Haioun C, Coiffier B, et al. Survival effect of darbepoetin alfa in patients with diffuse large B-cell lymphoma (DLBCL) treated with immunochemotherapy: The LNH03-6B study. J Clin Oncol. 2011;29: Abstract 9048.
  30. Nitz U, Gluz O, Oberhoff C, et al. Adjuvant chemotherapy with or without darbepoetin alpha in node-positive breast cancer: survival and quality of life analysis from the prospective randomized WSG ARA plus trial. Cancer Res. 2012;71(24 Suppl):PD07-06. doi: 10.1158/0008-5472.sabcs11-pd07-06.
  31. National Institute for Health and Care Excellence. Health Technology Appraisal Programme. Equality impact assessment – Guidance development. MTA Erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating anaemia in people having cancer treatment (including review of TA142). [Internet] Available from: https://www.nice.org.uk/guidance/ta323/documents/anaemia-cancertreatment-induced-erythropoiesisstimulating-agents-epoetin-and-darbepoetin-inc-rev-ta142-equality-impact-assessment-guidance-development2. (accessed 06.06.2016).
  32. Aapro M, Osterborg A, Gascon P, et al. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of i.v. iron. Ann Oncol. 2012;23(8):1954–62. doi: 10.1093/annonc/mds112.
  33. Beale AL, Penney MD, Allison MC. The prevalence of iron deficiency among patients presenting with colorectal cancer. Colorectal Dis. 2005;7(4):398–402. doi: 10.1111/j.1463-1318.2005.00789.x.
  34. Kuvibidila S, Gauthier T, Rayford W. Increased levels of serum transferrin receptor and serum transferrin receptor/log ferritin ratios in men with prostate cancer and the implications for body-iron stores. J Lab Clin Med. 2004;144(4):176–82. doi: 10.1016/j.lab.2004.03.017.
  35. Steinmetz HT, Tsamaloukas A, Schmitz S, et al. A new concept for the differential diagnosis and therapy of anaemia in cancer patients. Supp Care Cancer. 2010;19(2):261–9. doi: 10.1007/s00520-010-0812-2.
  36. Beguin Y, Lybaert W, Bosly A. A prospective observational study exploring the impact of iron status on response to darbepoetin alfa in patients with chemotherapy induced anemia. Blood. 2009;114(22): Abstract 2007.
  37. Ludwig H, Muldur E, Endler G, et al. High prevalence of iron deficiency across different tumors correlates with anemia, increases during cancer treatment and is associated with poor performance status. Haematologica. 2011;96: Abstract 982.
  38. Dangsuwan P, Manchana T. Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecol Oncol. 2010;116(3):522–5. doi: 10.1016/j.ygyno.2009.12.004.
  39. Kim YT, Kim SW, Yoon BS, et al. Effect of intravenously administered iron sucrose on the prevention of anemia in the cervical cancer patients treated with concurrent chemoradiotherapy. Gynecol Oncol. 2007;105(1):199–204. doi: 10.1016/j.ygyno.2006.11.014.
  40. Steinmetz HT. The role of intravenous iron in the treatment of anemia in cancer patients. Ther Adv Hematol. 2012;3(3):177–91. doi: 10.1177/ 2040620712440071.
  41. Henry DH. Parenteral Iron Therapy in Cancer-Associated Anemia. Hematology. 2010;2010(1):351–6. doi: 10.1182/asheducation-2010.1.351.
  42. Auerbach M, Silberstein PT, Webb RT, et al. Darbepoetin alfa 300 or 500 mg once every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. Am J Hematol. 2010;85(9):655–63. doi: 10.1002/ajh.21779.
  43. Bastit L, Vandebroek A, Altintas S, et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapy-induced anemia. J Clin Oncol. 2008;26(10):1611–8. doi: 10.1200/jco.2006.10.4620.
  44. Henry DH, Dahl NV, Auerbach M, et al. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. The Oncologist. 2007;12(2):231–42. doi: 10.1634/theoncologist.12-2-231.
  45. Pedrazzoli P, Farris A, Del Prete S, et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J Clin Oncol. 2008;26(10):1619–25. doi: 10.1200/jco.2007.12.2051.
  46. Steensma DP, Sloan JA, Dakhil SR, et al. Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy-associated anemia. J Clin Oncol. 2011;29(1):97–105. doi: 10.1200/jco.2010.30.3644.
  47. Beguin Y, Maertens J, De Prijck B, et al. Darbepoetin-alfa and I.V. iron administration after autologous hematopoietic stem cell transplantation: a prospective randomized multicenter trial. Am J Hematol. 2013;88(12):990–6. doi: 10.1002/ajh.23552.
  48. Hedenus M, Birgegard G, Nasman P, et al. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study. Leukemia. 2007;21:627–32. doi: 10.1038/sj.leu.2404562.
  49. Gafter-Gvili A, Rozen-Zvi B, Vidal L, et al. Intravenous iron supplementation for the treatment of cancer-related anemia—systematic review and meta-analysis. Acta Oncologica. 2013;52(1):18–29. doi: 10.3109/0284186x.2012.702921.
  50. Petrelli F, Borgonovo K, Cabiddu M, et al. Addition of iron to erythropoiesis-stimulating agents in cancer patients: a meta-analysis of randomized trials. J Cancer Res Clin Oncol. 2012;138(2):179–87. doi: 10.1007/s00432-011-1072-3.
  51. Сельчук В.Ю., Чистяков С.С., Толокнов Б.О. и др. Железодефицитная анемия: современное состояние проблемы. Русский медицинский журнал. 2012;3(1):1–8.
    [Sel’chuk VYu, Chistyakov SS, Toloknov BO, et al. Iron-deficiency anemia: state-of-the-art of the problem. Russkii meditsinskii zhurnal. 2012;3(1):1–8. (In Russ)]

Taxonomic Structure and Antibiotic Resistance of Bloodstream Infection Pathogens in Oncohematological Patients

INFECTIONS IN ONCOHEMATOLOGY , , , , , ,

NS Bagirova

N.N. Blokhin Russian Cancer Research Center, 24 Kashirskoye sh., Moscow, Russian Federation, 115478

For correspondence: Natal’ya Sergeevna Bagirova, DSci, 24 Kashirskoye sh., Moscow, Russian Federation, 115478; Tel.: +7(499)324-18-60; e-mail: nbagirova@mail.ru

For citation: Bagirova NS. Taxonomic Structure and Antibiotic Resistance of Bloodstream Infection Pathogens in Oncohematological Patients. Clinical oncohematology. 2015;8(2):191–200 (In Russ).

ABSTRACT

Background & Aims. In oncohematology, infections are one of main causes of morbidity and mortality in patients with hematological malignancies. Changing epidemiological patterns of infections in patients with hematological malignancies are characterized not only by the appearance of new pathogens of bloodstream infections, but also by the growth of pathogens resistant to antimicrobial drugs. It is important to conduct constant monitoring of taxonomic structure of bloodstream infections pathogens and their antimicrobial resistance in order to ensure adequate and timely treatment of severe infections. The aim of the study is the following: analysis of the taxonomic structure of pathogens isolated while diagnosing bacteremia in adult cancer patients using modern devices taking into account efficacy of the therapy of severe infections.

Methods. A microbiological study of blood samples of adult patients with hematological malignancies was carried out over the period from 2005 till 2013, if sepsis and other severe infections were suspected. Bacteremia was diagnosed using hematological analyzer/incubator Bactec FX400 (Becton Dickinson, USA) and Bact/Alert (BioMerieux, France), identification of strains was done using mass-spectrometer MALDI-TOF Microflex LT (Biotyper, Bruker Daltonics, Germany). Antimicrobial susceptibility was determined using automatic analyzers Microscan Walk Away 40/96+ (Siemens, Germany) and Vitek 2 (BioMerieux, France). Comparative data of foreign researchers are presented.

Results. 3794 blood cultures were obtained, 600 of which (15.8 %) demonstrated growth. Of 392 strains, only 210 (53.6 %) strains were considered true causative agents of bacteremia. No statistically significant differences in the frequency of isolation of Gram-positive cocci (47.6 %) and Gram-negative rods (39.5 %) were found. Fungi were significantly less common than Gram-positive cocci and Gram-negative rods (9 %; p < 0.0001). Other microorganisms constituted 3.8 %.

Conclusion. Therapy and prevention of infectious complications in adult patients with hematological malignancies are accompanied by development of growing antibiotic resistance of pathogens. Changes in taxonomic structure of pathogens of bloodstream infections should be taken into account when prescribing the empirical and etiotropic treatment.

Keywords: infections, cancer, bloodstream infections, bacteriemia, antimicrobial resistance, oncohematological disorders, antimicrobial therapy.

Received: January 12, 2015

Accepted: January 30, 2015

Read in PDF (RUS)pdficon

REFERENCES

  1. European Centre for Disease Prevention and Control (ECDC). Annual epidemiological report on communicable diseases in Europe 2008. Stockholm: ECDC; 2008.
  2. Pien BC, Sundaram P, Raoof N, et al. The clinical and prognostic importance of positive blood cultures in adults. Am J Med. 2010;123(9):819–28. doi: 10.1016/j.amjmed.2010.03.021.
  3. Dreyer AW. Blood Culture Systems: From Patient to Result. In: Azevedo L, ed. Sepsis – An Ongoing and Significant Challenge. InTech; 2012. pp. 287–310. doi: 10.5772/2958.
  4. Dellinger RP, Carlet JM, Masur H, et al. Surviving sepsis campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32(3):858–73. doi: 10.1097/01.ccm.0000117317.18092.e4.
  5. Kumar A, Roberts D, Wood KE, et al. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Crit Care Med. 2006;34(6):1589–96. doi: 10.1097/01.ccm.0000217961.75225.e9.
  6. Girmenia C, Menichetti F. Current Epidemiology and Prevention of Infectious Complications in Cancer Patients. Eur Oncol Haematol. 2011;7(4):270–7. doi: 10.17925/eoh.2011.07.04.270.
  7. Baron EJ, Miller JM, Weinstein MP, et al. A guide to utilization of the microbiology laboratory for diagnosis of infectious diseases: 2013 recommendations by the Infectious Diseases Society of America (IDSA) and the American Society for Microbiology (ASM)a. Clin Infect Dis. 2013;57(4): e22–e121. doi: 10.1093/cid/cit278.
  8. Багирова Н.С. Микробиологическая диагностика и рациональные подходы к терапии сепсиса у онкогематологических больных: Автореф. ¼ д-ра мед. наук. М., 2003. 274 с.
    [Bagirova NS. Mikrobiologicheskaya diagnostika i ratsional’nye podkhody k terapii sepsisa u onkogematologicheskikh bol’nykh. (Microbiological diagnosing and rational approaches to therapy of sepsis in oncohematological patients.) [dissertation] Moscow; 2003. 274 p. (In Russ)]
  9. Багирова Н.С., Дмитриева Н.В. Микробиологическая диагностика бактериемии. Пособие для врачей. М.: Министерство здравоохранения Российской Федерации, 2004. 35 с.
    [Bagirova NS, Dmitrieva NV. Mikrobiologicheskaya diagnostika bakteriemii. Posobie dlya vrachei. (Microbiological diagnosing of bacteriemia. Manual for physicians.) Moscow: Ministerstvo zdravookhraneniya Rossiiskoi Federatsii Publ.; 2004. 35 p. (In Russ)]
  10. Багирова Н.С. Современное состояние диагностики бактериемии. Сопроводительная терапия в онкологии. 2006;3:23–38.
    [Bagirova NS. State-of-the-art diagnostics of bacteriemia. Soprovoditel’naya terapiya v onkologii. 2006;3:23–38. (In Russ)]
  11. Laupland KB, Deirdre CL. Population-Based Epidemiology and Microbiology of сommunity-Onset Bloodstream Infections. Clin Microbiol Rev. 2014;27(4):647–64. doi: 10.1128/cmr.00002-14.
  12. Molnar Z, Fogas J. Timing IgM treatment in sepsis: is procalcitonin the answer? In: Vincent J-L, ed. Annual update in intensive care and emergency medicine 2012. Springer; 2012. pp. 109–15.
  13. Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the Infectious Diseases Society of America (IDSA Guidelines). Clin Infect Dis. 2011;52(4):e56–e93. doi: 10.1093/cid/cir073.
  14. European Centre for Disease Prevention and Control (ECDC). Annual epidemiological report on communicable diseases in Europe 2009. Stockholm, European Centre for Disease Prevention and Control (Surveillance Report – 2.6 Antimicrobial resistance and healthcare-associated infections); 2010. рр. 167–78.
  15. Bagirova N, Dmitrieva N. Bacteriemia in patients with hematological malignancies. J Clin Microbiol Infect Dis. 2005;11(Suppl 2):678.
  16. Bal AM, Garau J, Gould IM, et al. Vancomycin in the treatment of meticillin-resistant Staphylococcus auseus (MRSA) infection: End or an era? J Glob Antimic Resist. 2013;1(1):23–30. doi: 10.1016/j.jgar.2013.01.002.
  17. Peel T, Cheng AC, Spelman T, et al. Differing risk factor for vancomycin-resistant and vancomycin-sensitive enterococcal bacteraemia. J Clin Microbiol Infect Dis. 2011;18(4):388–94. doi: 10.1111/j.1469-0691.2011.03591.x.
  18. Kim YJ, Kim SI, Hong KW, et al. Carbapenem-resistant Acinetobacter baumannii: diversity of resistant mechanism and risk factor for infection. Epidemiol Infect. 2012;140(1):137–45. doi: 10.1017/s0950268811000744.
  19. Vila J, Pachon J. Acinetobacter baumannii resistant to everything: what should we do? J Clin Microbiol Infect Dis. 2011;17(7):955–6. doi: 10.1111/j.1469-0691.2011.03566.x.
  20. Villa-Fares X, Garcia de La Maria C, Lopez-Rojas R, et al. In vitro activity of several antimicrobial peptides against colistin-susceptible and colistin-resistant Acinetobacter baumannii. J Clin Microbiol Infect Dis. 2011;18(4):383–7. doi: 10.1111/j.1469-0691.2011.03581.x.
  21. Bagirova NS, Dmitrieva NV, Blokhin NN. Yeasts in patients (PTS) with hematologic malignancies (HM). Intern J Infect Dis. 2002;6(Suppl 2):S45. doi: 10.1016/s1201-9712(02)90273-0.
  22. Pfaller MA, Diekema DJ. Progress in antifungal susceptibility testing of Candida spp. by use of Clinical and Laboratory Standards Institute broth microdilution methods, 2010 to 2012. J Clin Microbiol. 2012;50(9):2846–56. doi: 10.1128/jcm.00937-12.
  23. Ranque S, Lachaud L, Gari-Toussaint M, et al. Interlaboratory reproducibility of Etest amphotericin B and caspofungin yeast susceptibility testing and comparison with the CLSI method. J Clin Microbiol. 2012;50(7):2305–9. doi: 10.1128/jcm.00490-12.
  24. Rangaraj G, Granwehr BP, Jiang Y, et al. Perils of quinolone exposure in cancer patients: breakthrough bacteremia with multidrug-resistant organisms. Cancer. 2010;116(4):967–73. doi: 10.1002/cncr.24812.

Influence of chemotherapy on reproductive system: methods of protection and preservation of ovarian function

REVIEWS , , , ,

M.V. Volochayeva1, R.G. Shmakov1, and Ye.A. Demina2

1 V.I. Kulakov Research Center of Obstetrics, Gynecology, and Perinatology, RF Ministry of Health, Moscow, Russian Federation

2 N.N. Blokhin Russian Cancer Research Centre, RAMS, Moscow, Russian Federation

ABSTRACT

The recent studies showed the great importance of discussing the issue of protection and preservation of the ovarian function in cancer patients. Nowadays, when new effective methods of treatment are available, many cancer patients wish to realize their reproductive function. In this review, we discuss the methods of ovarian protection such as pharmacological protection and IVF program including a cryopreservation and transplantation of ovarian tissue or cryopreservation of oocytes and embryos.

Keywords: fertility preservation, cancer, cryopreservation tissue, oocytes, embryos

Read in PDF (RUS)pdficon

REFERENCES

  1. Демина Е.А., Махова Е.Е., Сусулева Н.А., Ильященко В.А. Возможности сохранения детородной функции у женщин с лимфомой Ходжкина. РМЖ 2005; 1: 26–8.[Demina Ye.A., Makhova Ye.Ye., Susuleva N.A., and Ilyashchenko V.A. Potentials for preservation of reproductive function in females with Hodgkin’s lymphoma. RMZh 2005: 1:26–8. (In Russ.)].
  2. Шмаков Р.Г. Репродуктивное здоровье женщин с онкогематологическими заболеваниями: Автореф. дис. … д-ра мед. наук. М., 2008.[Shmakov R.G. Reproduktivnoye zdorove zhenshchin s onkogematologicheskimi zabolevaniyami. Dokt. diss. (Reproductive health in women with hematological malignancies : Dr. med. sci. diss.). M., 2008.]
  3. Maltaris T., Seufert R., Fischl F. et al. The effect of cancer treatment on female fertility and strategies for preserving fertility. Eur. J. Obstet. Gynecol. Reprod. Biol. 2007; 130: 148–55.
  4. Blumenfeld Z. Ovarian rescue/protection from chemotherapeutic agents. J. Soc. Gynecol. Investig. 2001; 8: 60–4.
  5. Blumenfeld Z. Reservation of fertility and ovarian function and minimalization of chemotherapy associated gonadotoxicity and premature ovarian failure: the role of inhibin-A and -B as markers. Mol. Cell. Endocrinol. 2002; 187: 93–105.
  6. Minton S.E., Munster P.N. Chemotherapy-induced amenorrhea and fertility in women undergoing adjuvant treatment for breast cancer. Cancer Control 2002; 9: 466–72.
  7. Mrozek E., Shapiro C.L. Survivorship and complications of treatment in breast cancer. Clin. Adv. Hematol. Oncol. 2005; 3: 211–22.
  8. Friedman D.L., Constine L.S. Late effects of treatment for Hodgkin lymphoma. J. Natl. Compr. Cancer Network 2006; 4: 249–57.
  9. Haukvik U.K., Dieset I., Bjoro T. et al. Treatment-related premature ovarian failure as a long-term complication after Hodgkin’s lymphoma. Ann. Oncol. 2006; 17: 1428–33.
  10. Behringer K., Mueller H., Goergen H. et al. Gonadal function and fertility in survivors after Hodgkin lymphoma treatment within the German Hodgkin Study Group HD13 to HD15 trials. J. Clin. Oncol. 2013; 31: 231–9.
  11. De Bruin M.L., Huisbrink J., Hauptmann M. et al. Treatment-related risk factors for premature menopause following Hodgkin lymphoma. Blood 2008; 111: 101–8.
  12. Van der Kaaij M.A., van Echten-Arends J., Simons A.H. et al. Fertility preservation after chemotherapy for Hodgkin lymphoma. Hematol. Oncol. 2010; 28: 168–79.
  13. Fornier M.N., Modi S., Panageas K.S. et al. Incidence of chemotherapy induced, long-term amenorrhea in patients with breast carcinoma age 40 years and younger after adjuvant anthracycline and taxane. Cancer 2005; 104: 1575–9.
  14. Behringer K., Breuer K., Reineke T. et al. Secondary amenorrhea after Hodgkin’s lymphoma is influenced by age at treatment, stage of disease, chemotherapy regimen, and the use of oral contraceptives during therapy: a report from the German Hodgkin’s Lymphoma Study Group. J. Clin. Oncol. 2005; 23: 7555–64.
  15. Gerber B., Dieterich M., Muеller H. et al. Controversies in preservation of ovary function and fertility in patients with breast cancer. Breast Cancer Res. Treat. 2008; 108: 1–7.
  16. Okanami Y., Ito Y., Watanabe C. et al. Incidence of chemotherapy induced amenorrhea in premenopausal patients with breast cancer following adjuvant anthracycline and taxane. Breast Cancer 2011; 18: 182–8.
  17. Lee S.J., Schover L.R., Partridge A.H. et al. American Society of Clinical Oncology recommendations on fertility preservation in cancer patients. J. Clin. Oncol. 2006; 24: 2917–31.
  18. Tham Y.L., Sexton K., Weiss H. et al. The rates of chemotherapy induced amenorrhea in patients treated with adjuvant doxorubicin and cyclophosphamide followed by a taxane. Am. J. Clin. Oncol. 2007; 30: 126–32.
  19. Sklar C.A., Mertens A.C., Mitby P. et al. Premature menopause in survivors of childhood cancer: a report from the childhood cancer survivor study. J. Natl. Cancer Inst. 2006; 98: 890–6.
  20. Dillon K.E., Sammel M.D., Prewitt M. et al. Pretreatment antimullerian hormone levels determine rate of post therapy ovarian reserve recovery: acute changes in ovarian reserve during and after chemotherapy. Fertil. Steril. 2013; 99: 477–83.
  21. Wallace W.H., Thomson A.B., Saran F. et al. Predicting age of ovarian failure after radiation to a field that includes the ovaries. Int. J. Radiat. Oncol. Biol. Phys. 2005; 62: 738–44.
  22. Knauff E.A., Eijkemans M.J., Lambalk C.B. et al. Anti-Mullerian hormone, inhibin B, and antral follicle count in young women with ovarian failure. J. Clin. Endocrinol. Metab. 2009; 94: 786–92.
  23. Iwase A., Sugita A., Hirokawa W. et al. Anti-Mullerian hormone as a marker of ovarian reserve following chemotherapy in patients with gestational trophoblastic neoplasia. Eur. J. Obstet. Gynecol. Reprod. Biol. 2013; 167: 194–8.
  24. Munster P.N., Moore A.P., Ismail-Khan R. et al. Randomized trial using gonadotropin-releasing hormone agonist triptorelin for the preservation of ovarian function during (neo)adjuvant chemotherapy for breast cancer. J. Clin. Oncol. 2012; 30: 533–8.
  25. Recchia F., Saggio G., Amiconi G. et al. Gonadotropin-releasing hormone analogues added to adjuvant chemotherapy protect ovarian function and improve clinical outcomes in young women with early breast carcinoma. Cancer 2006; 106: 514–23.
  26. Han S.S., Kim Y.H., Lee S.H. et al. Underuse of ovarian transposition in reproductive-aged cancer patients treated by primary or adjuvant pelvic irradiation. J. Obstet. Gynaecol. Res. 2011; 37: 825–9.
  27. Pentheroudakis G., Pavlidis N., Castiglione M. Cancer, fertility and pregnancy: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann. Oncol. 2009; 20: 178–81 (Suppl. 4).
  28. Donnez J., Dolmans M.M. Cryopreservation and transplantation of ovarian tissue. Clin. Obstet. Gynecol. 2010; 53: 787–96.
  29. Bedaiwy M.A., Abou-Setta A.M., Desai N. et al. Gonadotropin-releasing hormone analog cotreatment for preservation of ovarian function during gonadotoxic chemotherapy: A systematic review and meta-analysis. Fertil. Steril. 2011; 95: 906–14, e1–4.
  30. Blumenfeld Z., von Wolff M. GnRH analogues and oral contraceptives for fertility preservation in women during chemotherapy. Hum. Reprod. Update 2008; 14: 543–52.
  31. Демина Е.А., Перилова Е.Е., Шмаков Р.Г. Использование комбинированных пероральных контрацептивов для профилактики повреждения функции яичников у больных лимфомой Ходжкина. М., 2004: 1352–4. [Demina Ye.A., Perilova Ye.Ye., Shmakov R.G. Ispolzovaniye kombinirovannykh peroralnykh kontratseptivov dlya profilaktiki povrezhdeniya funktsii yaichnikov u bolnykh limfomoy Khodzhkina (Use of oral contraceptives for prevention of ovarian function damage in patients with Hodgkin’s lymphoma). M., 2004: 1352–4.]
  32. Blumenfeld Z., Avivi I., Linn S. et al. Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy. Hum. Reprod. 1996; 11: 1620–6.
  33. Badawy A., Elnashar A., El-Ashry M. et al. Gonadotropin-releasing hormone agonists for prevention of chemotherapy-induced ovarian damage: prospective randomized study. Fertil. Steril. 2009; 91: 694–7.
  34. Sverrisdottir A., Nystedt M., Johansson H. et al. Adjuvant goserelin and ovarian preservation in chemotherapy treated patients with early breast cancer: results from a randomized trial. Breast Cancer Res. Treat. 2009; 117: 561–7.
  35. Clowse M.E., Behera M.A., Anders C.K. et al. Ovarian preservation by GnRH agonists during chemotherapy: a meta-analysis. J. Womens Health 2009; 18: 311–9.
  36. Del Mastro L., Boni L., Michelotti A. et al. Effect of the gonadotropinreleasing hormone analogue triptorelin on the occurrence of chemotherapyinduced early menopause in premenopausal women with breast cancer: a randomized trial. JAMA 2011; 306: 269–76.
  37. Chen H., Li J., Cui T. et al. Adjuvant gonadotropin-releasing hormone analogues for the prevention of chemotherapy induced premature ovarian failure in premenopausal women. Cochrane Database Syst Rev 2011; 9: CD008018.
  38. Wong M., O’Neill S., Walsh G. et al. Goserelin with chemotherapy to preserve ovarian function in pre-menopausal women with early breast cancer: menstruation and pregnancy outcomes. Ann. Oncol. 2013; 24: 133–8.
  39. Yang B., Shi W., Yang J. et al. Concurrent treatment with gonadotropinreleasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: A meta-analysis of randomized controlled trials. Breast 2013; 22: 150–7.
  40. Leonard R.C., Adamson D., Anderson R. et al. The OPTION trial of adjuvant ovarian protection by goserelin in adjuvant chemotherapy for early breast cancer. J. Clin. Oncol. 2010; 28: Abstract 590.
  41. Gerber B., von Minckwitz G., Stehle H. et al. Effect of luteinizing hormonereleasing hormone agonist on ovarian function after modern adjuvant breast cancer chemotherapy: the GBG 37 ZORO study. J. Clin. Oncol. 2011; 29: 2334–41.
  42. Elgindy E.A., El-Haieg D.O., Khorshid O.M. et al. Gonadatrophin suppression to prevent chemotherapy-induced ovarian damage: a randomized controlled trial. Obstet. Gynecol. 2013; 121: 78–86.
  43. American Society for Reproductive Medicine. http://www.asrm.org
  44. Azim A.A., Costantini-Ferrando M., Oktay K. Safety of fertility preservation by ovarian stimulation with letrozole and gonadotropins in patients with breast cancer: A prospective controlled study. J. Clin. Oncol. 2008; 26: 2630–5.
  45. Oktay K., Buyuk E., Libertella N. et al. Fertility preservation in breast cancer patients: A prospective controlled comparison of ovarian stimulation with tamoxifen and letrozole for embryo cryopreservation. J. Clin. Oncol. 2005; 23: 4347–53.
  46. Lee S., Oktay K. Does higher starting dose of FSH stimulation with letrozole improve fertility preservation outcomes in women with breast cancer? Fertil. Steril. 2012; 98: 961.e1–4.e1.
  47. Sonmezer M., Turkcuoglu I., Coskun U., Oktay K. Random-start controlled ovarian hyperstimulation for emergency fertility preservation in letrozole cycles. Fertil. Steril. 2011; 95: 2125.e9–11.
  48. Isachenko V., Isachenko E., Keck G. et al. First live birth in Germany after re-transplantation of cryopreserved ovarian tissue: Original device for initiation of ice formation. Clin. Lab. 2012; 58: 933–8.
  49. Bacigalupo A., Ballen K., Rizzo D. et al. Defining the intensity of conditioning regimens: Working definitions. Biol. Blood Marrow Transplant. 2009; 15: 1628–33.
  50. Borini A., Bianchi V. Cryopreservation of mature and immature oocytes. Clin. Obstet. Gynecol. 2010; 53: 763–74.
  51. Huang J.Y., Chian R.C., Gilbert L. et al. Retrieval of immature oocytes from unstimulated ovaries followed by in vitro maturation and vitrification: A novel strategy of fertility preservation for breast cancer patients. Am. J. Surg. 2010; 200: 177–83.
  52. Rudick B., Opper N., Paulson R. et al. The status of oocyte cryopreservation in the United States. Fertil. Steril. 2010; 94: 2642–6.
  53. Demeestere I., Simon P., Emiliani S., Delbaere A., Englert Y. Orthotopic and heterotopic ovarian tissue transplantation. Hum. Reprod. Update 2009; 15: 649–65.
  54. Demeestere I., Moffa F., Peccatori F., Poirot C., Shalom-Paz E. Multiple approaches for individualized fertility protective therapy in cancer patients. Obstet. Gynecol. Int. 2012: 495142 (Medline Abstract).
  55. Oktay K., Cil A.P., Bang H. Efficiency of oocyte cryopreservation: A metaanalysis. Fertil. Steril. 2006; 86: 70–80.
  56. Donnez J., Squifflet J., Jadoul P. et al. Pregnancy and live birth after autotransplantation of frozen-thawed ovarian tissue in a patient with metastatic disease undergoing chemotherapy and hematopoietic stem cell transplantation. Fertil. Steril. 2011; 95: 1787.e1–4.
  57. Kim M.K., Lee D.R., Han J.E. et al. Live birth with vitrified-warmed oocytes of a chronic myeloid leukemia patient nine years after allogenic bone marrow transplantation. J. Assist. Reprod. Genet. 2011; 28: 1167–70.
  58. Dittrich R., Lotz L., Keck G. et al. Live birth after ovarian tissue autotransplantation following overnight transportation before cryopreservation. Fertil. Steril. 2012; 97: 387–90.
  59. Andersen C.Y., Silber S.J., Berghold S.H. et al. Long-term duration of function of ovarian tissue transplants: Case reports. Reprod. Biomed. Online 2012; 25: 128–32.
  60. Oktay K., Rodriguez-Wallberg K.A. Four spontaneous pregnancies and three live births following subcutaneous transplantation of frozen banked ovarian tissue: What is the explanation? Fertil. Steril. 2011; 95: 804.e7–10.
  61. Meirow D., Levron J., Eldar-Geva T. et al. Pregnancy after transplantation of cryopreserved ovarian tissue in a patient with ovarian failure after chemotherapy. N. Engl. J. Med. 2005; 353: 318–21.
  62. Anderson R.A., Wallace W.H., Baird D.T. Ovarian cryopreservation for fertility preservation: Indications and outcomes. Reproduction 2008; 136: 681–9.
  63. Reebals J.F., Brown R., Buckner E.B. Nurse practice issues regarding sperm banking in adolescent male cancer patients. J. Pediatr. Oncol. Nurs. 2006; 23: 182–8.
  64. Keros V., Hultenby K., Borgstrumlom B. et al. Methods of cryopreservation of testicular tissue with viable spermatogonia in pre-pubertal boys undergoing gonadotoxic cancer treatment. Hum. Reprod. 2007; 22: 1384–95.
  65. Jadoul P., Dolmans M.M., Donnez J. Fertility preservation in girls during childhood: Is it feasible, efficient and safe and to whom should it be proposed? Hum. Reprod. Update 2010; 16: 617–30.
  66. Cvancarova M., Samuelsen S.O., Magelssen H. et al. Reproduction rates after cancer treatment: Experience from the Norwegian radium hospital. J. Clin. Oncol. 2009; 27: 334–43.
  67. Nieman C.L., Kinahan K.E., Yount S.E. et al. Fertility preservation and adolescent cancer patients: Lessons from adult survivors of childhood cancer and their parents. Cancer Treat. Res. 2007; 138: 201–17

Anemias and iron deficiency in cancer patients

ANEMIAS , , , ,

V.V. Ptushkin

Federal Scientific and Clinical Centre of Pediatric Hematology, Oncology and Immunology named after Dmitriy Rogachev, Moscow, Russian Federation

ABSTRACT

Anemia is frequent in cancer patients and its incidence increases with chemotherapy. Anemia negatively impacts survival and accentuates fatigue in cancer patients. Cancer promotes inflammatory cytokine production, which suppresses erythropoiesis and erythropoietin production. Erythropoiesis-stimulating agents improve erythropoiesis and reduce transfusion needs in anemic cancer patients receiving chemotherapy. However, meta-analyses have shown an increased risk of thromboembolic events with еrythropoiesis-stimulating agents use during chemotherapy, but not increased on-study mortality or reduced overall survival. Inflammatory cytokine production in patients with cancer, reduce the availability of iron for effective erythropoiesis. This review summarises clinical consequences of iron deficiency and anaemia in cancer patients, mechanisms how impaired iron homeostasis affects diagnosis and treatment of iron deficiency, and data from clinical trials evaluating i.v. iron with or without concomitant erythropoiesis-stimulating agents.

Keywords: Anemia, cancer, erythropoietin, iron propagates, ferric carboxymaltose, ferritin, transferrin

Read in PDF (RUS)pdficon

REFERENCES

  1. Ludwig H., Van B.S., Barrett-Lee P. et al. The European Cancer AnaemiaSurvey (ECAS): a large, multinational, prospective survey defining the prevalence, incidence, and treatment of anaemia in cancer patients. Eur. J. Cancer 2004; 40: 2293–306.
  2. Groopman J.E., Itri L.M. Chemotherapy-induced anemia in adults: incidence and treatment. J. Natl. Cancer Inst. 1999; 91: 1616–34.
  3. Beale A.L., Penney M.D., Allison M.C. The prevalence of iron deficiency among patients presenting with colorectal cancer. Colorectal. Dis. 2005; 7: 398–402.
  4. Kuvibidila S.R., Gauthier T., Rayford W. Serum ferritin levels and transferrin saturation in men with prostate cancer. J. Natl. Med. Assoc. 2004; 96: 641–9.
  5. Steinmetz H.T., Tsamaloukas A., Schmitz S. et al. A new concept for the differential diagnosis and therapy of anaemia in cancer patients. Support Care Cancer 2010; 19: 261–9.
  6. Beguin Y., Lybaert W., Bosly A. A prospective observational study exploring the impact of iron status on response to darbepoetin alfa in patients with chemotherapy induced anemia. Blood 2009; 114 (Abstr 2007).
  7. Ludwig H., Muldur E., Endler G. et al. High prevalence of iron deficiency across different tumors correlates with anemia, increases during cancer treatment and is associated with poor performance status. Haematologica 2011; 96 (Abstr 982).
  8. Anker S.D., Comin C.J., Filippatos G. et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N. Engl. J. Med. 2009; 361: 2436–48.
  9. Crawford J., Cella D., Cleeland C.S. et al. Relationship between changes in hemoglobin level and quality of life during chemotherapy in anemic cancer patients receiving epoetin alfa therapy. Cancer 2002; 95: 888–95.
  10. Auerbach M., Ballard H., Trout J.R. et al. Intravenous iron optimizes the response to recombinant human erythropoietin in cancer patients with chemotherapy-related anemia: a multicenter, open-label, randomized trial. J. Clin. Oncol. 2004; 22: 1301–7.
  11. Rizzo J.D., Brouwers M., Hurley P. et al. American Society of Hematology/ American Society of Clinical Oncology clinical practice guideline update on the use of epoetin and darbepoetin in adult patients with cancer. Blood 2010; 116: 4045–59.
  12. Auerbach M., Silberstein P.T., Webb R.T. et al. Darbepoetin alfa 300 or 500 mg once every 3 weeks with or without intravenous iron in patients with chemotherapyinduced anemia. Am. J. Hematol. 2010; 85: 655–63.
  13. Henry D.H., Dahl N.V., Auerbach M. et al. Intravenous ferric gluconate significantly improves response to epoetin alfa versus oral iron or no iron in anemic patients with cancer receiving chemotherapy. Oncologist 2007; 12: 231–42.
  14. Pedrazzoli P., Farris A., Del P.S. et al. Randomized trial of intravenous iron supplementation in patients with chemotherapy-related anemia without iron deficiency treated with darbepoetin alpha. J. Clin. Oncol. 2008; 26: 1619–25.
  15. Beguin Y. Prediction of response and other improvements on the limitations of recombinant human erythropoietin therapy in anemic cancer patients. Haematologica 2002; 87: 1209–21.
  16. Wish J.B. Assessing iron status: beyond serum ferritin and transferrin saturation. Clin. J. Am. Soc. Nephrol. 2006; 1(Suppl. 1): S4–S8.
  17. Hedenus M., Birgegard G., Nasman P et al. Addition of intravenous iron to epoetin beta increases hemoglobin response and decreases epoetin dose requirement in anemic patients with lymphoproliferative malignancies: a randomized multicenter study. Leukemia 2007; 21: 627–32.
  18. Ludwig H., Endler G., Hubl W. et al. High prevalence of iron deficiency in patients with various hematological and malignant diseases: a single center study in 1989 sequential patients. Haematologica 2010; 95 (Abstr 1819).
  19. Ludwig H., Aapro M., Bokemeyer C. et al. Treatment patterns and outcomes in the management of anaemia in cancer patients in Europe: findings from the Anaemia Cancer Treatment (ACT) study. Eur. J. Cancer 2009; 45: 1603–15.
  20. Aapro M.S., Link H. September 2007 update on EORTC guidelines and anemia management with erythropoiesis-stimulating agents. Oncologist 2008; 13(Suppl. 3): 33–6.
  21. Vamvakas E.C., Blajchman M.A. Transfusion-related mortality: the ongoing risks of allogeneic blood transfusion and the available strategies for their prevention. Blood 2009; 113: 3406–17.
  22. Marik P.E., Corwin H.L. Efficacy of red blood cell transfusion in the critically ill: a systematic review of the literature. Crit. Care Med. 2008; 36: 2667–74.
  23. Thomson A., Farmer S., Hofmann A. et al. Patient blood management—a new paradigm for transfusion medicine? ISBT Sci. Series 2009; 4: 423–35.
  24. Amato A.C., Pescatori M. Effect of perioperative blood transfusions on recurrence of colorectal cancer: meta-analysis stratified on risk factors. Dis. Colon Rectum 1998; 41: 570–85.
  25. Bohlius J., Schmidlin K., Brillant C. et al. Erythropoietin or darbepoetin for patients with cancer—meta-analysis based on individual patient data. Cochrane Database Syst. Rev. 2009; CD007303.
  26. Gabrilove J.L., Cleeland C.S., Livingston R.B. et al. Clinical evaluation of once-weekly dosing of epoetin alfa in chemotherapy patients: improvements in hemoglobin and quality of life are similar to three-times-weekly dosing. J. Clin. Oncol. 2001; 19: 2875–82.
  27. Littlewood T.J., Bajetta E., Nortier J.W. et al. Effects of epoetin alfa on hematologic parameters and quality of life in cancer patients receiving nonplatinum chemotherapy: results of a randomized, double-blind, placebo-controlled trial. J. Clin. Oncol. 2001; 19: 2865–74.
  28. US Food and Drug Administration. Epoetin Alfa (Marketed as Epoetin, Procrit) Label. http://www.accessdata.fda.gov/drugsatfda_docs/ label/2010/103234s5199lbl.pdf (5 September 2011, date last accessed).
  29. US Food and Drug Administration. Darbepoetin Alfa (Marketed as Aransep) Label. http://www.accessdata.fda.gov/drugsatfda_docs/ label/2010/103951s5197lbl.pdf (5 September 2011, date last accessed).
  30. Macdougall I.C. Strategies for iron supplementation: oral versus intravenous. Kidney Int. Suppl. 1999; 69: S61–S66.
  31. Bastit L., Vandebroek A., Altintas S. et al. Randomized, multicenter, controlled trial comparing the efficacy and safety of darbepoetin alpha administered every 3 weeks with or without intravenous iron in patients with chemotherapyinduced anemia. J. Clin. Oncol. 2008; 26: 1611–8.
  32. Steensma D.P., Sloan J.A., Dakhil S.R. et al. Phase III, randomized study of the effects of parenteral iron, oral iron, or no iron supplementation on the erythropoietic response to darbepoetin alfa for patients with chemotherapy associated anemia. J. Clin. Oncol. 2011; 29: 97–105.
  33. Gafter-Gvili A., Rozen-Zvi B., Vidal L. et al. Intravenous iron supplementation for the treatment of cancer-related anemia—systematic review and metaanalysis. Blood 2010; 116 (Abstr 4249).
  34. Petrelli F., Borgonovo K., Cabiddu M. et al. Addition of iron to erythropoiesis-stimulating agents in cancer patients: a meta-analysis of randomized trials. J. Cancer Res. Clin. Oncol. 2012; 138: 179–87.
  35. Dangsuwan P., Manchana T. Blood transfusion reduction with intravenous iron in gynecologic cancer patients receiving chemotherapy. Gynecol. Oncol. 2010; 116: 522–5.
  36. Steinmetz T., Tschechne B., Virgin G. et al. Ferric carboxymaltose for the correction of cancer- and chemotherapy-associated anemia in clinical practice. Haematologica 2011; 96 (Abstr 983).
  37. Evstatiev R., Marteau P., Iqbal T. et al. FERGIcor, a randomized controlled trial on ferric carboxymaltose for iron deficiency anemia in inflammatory bowel disease. Gastroenterology 2011; 141: 846–53.
  38. Kulnigg S., Stoinov S., Simanenkov V. et al. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. Am. J. Gastroenterol. 2008; 103: 1182–92.
  39. Aapro M., Beguin Y., Birgegard G. et al. Too-low iron doses and too many dropouts in negative iron trial? J. Clin. Oncol. 2011; 29: e525–e526.
  40. Bailie G.R., Horl W.H., Verhof J.J. Differences in spontaneously reported hypersensitivity and serious adverse events for intravenous iron preparations: comparison of Europe and North America. Drug Res. 2011; 61: 267–75.
  41. Bailie G.R., Clark J.A., Lane C.E. et al. Hypersensitivity reactions and deaths associated with intravenous iron preparations. Nephrol. Dial. Transplant. 2005; 20: 1443–9.
  42. Chertow G.M., Mason P.D., Vaage-Nilsen O. et al. Update on adverse drug events associated with parenteral iron. Nephrol. Dial. Transplant. 2006; 21: 378–82.
  43. Zhang F., Wang W., Tsuji Y. et al. Post-transcriptional modulation of iron homeostasis during p53-dependent growth arrest. J. Biol. Chem. 2008; 283: 33911–8.
  44. Baliga R., Zhang Z., Baliga M. et al. In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int. 1998; 53: 394–401.
  45. Toyokuni S. Role of iron in carcinogenesis: cancer as a ferrotoxic disease. Cancer Sci. 2009; 100: 9–16.
  46. Bergeron R.J., Streiff R.R., Elliott G.T. Influence of iron on in vivo proliferation and lethality of L1210 cells. J. Nutr. 1985; 115: 369–74.
  47. Carthew P., Nolan B.M., Smith A.G. et al. Iron promotes DEN initiated GST-P foci in rat liver. Carcinogenesis 1997; 18: 599–603.
  48. Auerbach M., Glaspy J. What is the right balance between iron and erythropoiesis stimulating agents in chemotherapy induced anemia? Eur. J. Clin. Med. Oncol. 2009; 1: 7–12.
  49. Beguin Y., Maertens J., De Prijck B. et al. Darbepoetin-alfa and i.v. iron administration after autologous hematopoietic stem cell transplantation: a prospective randomized multicenter trial. Blood 2008; 112 (Abstr 54).