Earthworms: Sources of Antimicrobial and Anticancer Molecules

  • Edwin L. Cooper
  • Binggen Ru
  • Ning Weng
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 546)


According to Reynolds and Reynolds, (1972) few people know of the earthworm’s long association with medicine, yet documents recording its use in various remedies date back to 1340 A.D.1, 2 For instance, doctors practicing folk medicine in Burma and India use earthworms in treatment of various diseases. In Burma, the primary use for earthworms is in the treatment of a disease called ye se kun byo, which display the symptoms of pyorrhea. The worms are heated in a closed pot until reduced to ashes and these ashes are used either alone as a tooth powder, or for greater palatability, are combined with roasted tamarind seeds and betel nuts.3 With another disease meephwanoyeekhun thwaykhan, women generally feel postpartal weakness and are unable to nurse their infant. Worms are boiled in water with salt and onions and the clear fluid is decanted and mixed with the patient’s food.3 It is interesting to note that the patient is kept ignorant of the nature of the medicine!


Plasminogen Activator Serine Protease Fibrinolytic Activity Fibrinolytic Enzyme Coelomic Fluid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    J. W. Reynolds, W.M. Reynolds, Earthworms in Medicine, American Journal of Nursing, 72, 1273–1274. 1972.PubMedCrossRefGoogle Scholar
  2. 2.
    J. Stevenson, Oligochaeta. Claredon Press Oxford, 1930, pp. 658–659.Google Scholar
  3. 3.
    G.E. Gates, The Earthworms of Rangoon, J. Burma Res. Soc. 25, 196–221 (1926).Google Scholar
  4. 4.
    H.S. Bristowe, Insects and other invertebrates for human consumption in Siam, Trans. Entomol. Soc. 80, 387–404 (1932).CrossRefGoogle Scholar
  5. 5.
    L.G.K Carr, Interesting animal foods, medicines and omens of the eastern Indians, with comparisons to ancient European practices, J. Wash. Acad. Sci. 41, 229–235 (1951).Google Scholar
  6. 6.
    S. F. Price, Kentucky Folklore, J Am Folklore. 14, 30–38 (1901).CrossRefGoogle Scholar
  7. 7.
    The Eu Yan Sang Heritage An Anthology of Chinese Herbs and Medicines. Eu Yan Sang International Holdings Pte Ltd, 269A South Bridge Road, Singapore 05818.Google Scholar
  8. 8.
    R. Fan, The new medicine “lumbrokinase capsules” for treatment and prevention of thrombus and imbolicdiseases, pp. 1–7 [Institute of Biophysics, Academia Sinica, Beijing Bio Pharmaceuticals Co. Ltd. 15 Datun Road, Beijing 100101 CHINA] (Personal Communication through Dr. Z. Zhang, National Laboratory of Molecular Virology and Genetic Engineering, Beijing CHINA) (1996).Google Scholar
  9. 9.
    D.S. Linthicum, E.A. Stein, D.H. Marks, and E.L. Cooper, Electron microscopic observations of normal coelomocytes from the earthworm Lumbricus terrestris, Cell and Tissue Res., 185, 315–330 (1977).Google Scholar
  10. 10.
    E. A. Stein, R.R. Avtalion, and E.L. Cooper, The coelomocytes of the earthworm Lumbricus terrestris: morphology and phagocytic properties, J. Morphol 153, 467–477 (1977).PubMedCrossRefGoogle Scholar
  11. 11.
    E.A. Stein, A. Wojdani, and E.L. Cooper, Agglutinins in the earthworm Lumbricus terrestris: naturally occurring and induced, Dev. Comp. Immunol., 6, 407–421 (1982).PubMedCrossRefGoogle Scholar
  12. 12.
    E.A. Stein, S. Younai, and E.L. Cooper, Bacterial agglutinins of the earthworm Lumbricus terrestris, Comp. Biochem. Physiol, 84: 409–415.Google Scholar
  13. 13.
    E.A. Stein and E.L. Cooper, . In vitro agglutinin production by earthworm leukocytes, Dev. Comp. Immunol. 12, 531–547(1988).Google Scholar
  14. 14.
    E.A. Stein, A. Morovati, P. Rahimian, and E.L. Cooper, Lipid agglutinins from coelomic fluid of the earthworm Lumbricus terrestris, Comp. Biochem. Physiol, 94B, 703–707 (1989).Google Scholar
  15. 15.
    E.A. Stein, S. Younai, E.L. Cooper, Separation and partial purification of agglutinins from coelomic fluid of the earthworm, Lumbricus terrestris, Comp. Biochem. Physiol. 97, 701–705 (1990).Google Scholar
  16. 16.
    E.A. Stein, and E.L. Cooper, Cytochemical observations of coelomocytes from the earthworm, Lumbricus terrestris, J. Histochem, 10, 657–678 (1978).CrossRefGoogle Scholar
  17. 17.
    E.A. Stein, and E.L. Cooper, The role of opsonins in phagocytosis by coelomocytes of the earthworm, Lumbricus terrestris, Dev. Comp. Immunol. 5, 15–25 (1981).CrossRefGoogle Scholar
  18. 18.
    E.A. Stein, and E.L. Cooper, Carbohydrate and glycoprotein inhibitors of naturally occurring and induced agglutinins from the earthworm, Lumbricus terrestris, Comp. Biol. Chem. 76B, 197–206 (1983).Google Scholar
  19. 19.
    A. Wojdani, E.A. Stein, E.L. Cooper, and L.J. Alfred, Agglutinins and proteins in the earthworm, Lumbricus terrestris, before and after injection of erythrocytes, carbohydrates and other materials, Dev. Comp. Immunol. 6, 613–624(1982).PubMedGoogle Scholar
  20. 20.
    P. Roch, E.L. Cooper, and D.R Eskinazi, Serological evidences for a membrane structure related to human β2-microglobulin expressed by certain earthworm leukocytes, Eur. J. Immunol. 13, 1037–1042 (1983).PubMedCrossRefGoogle Scholar
  21. 21.
    A.H. Saad, and E.L. Cooper, Evidence for a Thy-1 like molecule expressed on earthworm leukocytes. Zool. Sci. 7, 217–222 (1990).Google Scholar
  22. 22.
    E.L. Cooper, A. Cossarizza, M.M. Suzuki, S. Salvioli, M. Capri, D. Quaglino, C. Franceschi, Autogeneic but not allogeneic earthworm effector coelomocytes kill the mammalian tumor target K562, Cell. Immunol. 166, 113–122(1995).Google Scholar
  23. 23.
    A. Cossarizza, E.L. Cooper, M.M. Suzuki, S. Salvioli, M. Capri, M., G. Gri, D. Quaglino, C. Franceschi, Earthworm leukocytes that are not phagocytic and cross-react with several human epitopes can kill human tumor cell lines, Exp. Cell Res. 224, 174–182 (1996).PubMedCrossRefGoogle Scholar
  24. 24.
    D. Quaglino, E.L. Cooper, S. Salvioli, M. Capri, M.M. Suzuki, I. Pasquali-Ronchetti, C. Franceschi, A. Cossarizza, Earthworm coelomocytes in vitro: cellular features and “granuloma” formation during cytotoxic activity against the mammalian tumor cell target K562, Eu. J. Cell Biol. 70, 278–288 (1996).Google Scholar
  25. 25.
    E. Kauschke, P. Pagliara, L. Stabili, E.L. Cooper, Characterization of proteolytic activity in coelomic fluid of Lumbricus terrestris L. (Annelida, Lumbricidae), Comp. Biochem. Physiol. 116B, 235–242 (1997).Google Scholar
  26. 26.
    S. Lange, F. Nussler, E. Kauschke, G. Lutsch, E.L. Cooper, A. Herrmann, Interaction of earthworm hemolysin with lipid membranes requires sphingolipids, J. Biol. Chem. 272, 20884–20892 (1997).PubMedCrossRefGoogle Scholar
  27. 27.
    S. Lange, E. Kauschke, W. Mohrig, E.L. Cooper, Biochemical characteristics of eiseniapore, a pore forming protein in the coelomic fluid of earthworms, Eur. J. Biochem. 263, 1–11 (1999).CrossRefGoogle Scholar
  28. 28.
    Ph. Roch, P. Ville, E.L. Cooper, Characterization of a 14 kDa plant-related serine protease inhibitor and regulation of cytotoxic activity in earthworm coelomic fluid, Dev. Comp. Immunol 22, 1–12 (1998).PubMedCrossRefGoogle Scholar
  29. 29.
    I. Eue, E. Kauschke, W. Mohrig, E.L. Cooper, Isolation and characterization of earthworm hemolysins and agglutinins, Dev. Comp. Immunol. 22, 13–25 (1998).PubMedCrossRefGoogle Scholar
  30. 30.
    V. Vetvicka, P. Sima, E.L. Cooper, M. Bilej, Ph. Roch, Immunology of Annelids (CRC Press, Boca Raton, 1994), p. 300.Google Scholar
  31. 31.
    E. Kauschke, and W. Mohrig, Cytotoxic activity in the coelomic fluid of the annelid Eiseniafoetida., J. Comp. Physiol. B. 157, 77–83 (1987).CrossRefGoogle Scholar
  32. 32.
    F. Hirigoyenberry, F. Lassalle, M. Lassegues, Antibacterial activity of Eisenia fetida andrei coelomic fluid: transcription and translation regulation of lysozyme and proteins evidenced after bacterial infestation., Comp. Biochem. Physiol. 95B, 71–75 (1987).Google Scholar
  33. 33.
    A. Wojdani, E.A. Stein, L.J Alfred, E. L. Cooper, Mitogenic effect of earthworm (Lumbricus terrestris) coelomic fluid on mouse and human lymphocytes, Immunobiology 166, 157–167 (1984).PubMedCrossRefGoogle Scholar
  34. 34.
    R. Hanusova, M Bilej, L. Brys, P. De Baetselier, A. Beschin, Identification of a coelomic mitogenic factor in Eisenia foetida earthworm, Immunol. Lett. 65, 203–311 (1990).CrossRefGoogle Scholar
  35. 35.
    M. Lassegues, A. Milochau, F. Doignon, L. Du Pasquier, P. Valembois, Sequence and expression of an Eisenia foetida derived cDNA clone that encodes the 40 kDa fetidin antibacterial protein, . Eur. J. Biochem. 246, 756–762 (1997).PubMedCrossRefGoogle Scholar
  36. 36.
    Ph. Roch, E.L Cooper, E.L. Invertebrate immune responses: cells and molecular products, Adv. Comp. Env. Physiol. 23, 116–145(1996).Google Scholar
  37. 37.
    P. Valembois, Ph. Roch, D. Boiledieu, in: Phylogeny of Immunological Memory, edited by M. J. Manning (Elsevier Biomedical Press, North-Holland, 1980), pp. 47–55.Google Scholar
  38. 38.
    P. Valembois, Ph Roch, L. Du Pasquier, in: Aspects of developmental and comparative immunology, edited by J. B. Solomon (Pergamon Press, Oxford, 1980), pp. 23–30.Google Scholar
  39. 39.
    E. L. Cooper, and Ph. Roch, Earthworm leukocyte interactions during early stages of graft rejection, J. Exp. Zool. 232, 67–72 (1984).PubMedCrossRefGoogle Scholar
  40. 40.
    F. Lassalle, M. Lassegues, Ph. Roch, Protein analysis of earthworm coelomic fluid. IV Evidence, activity, induction and purification of Eisenia fetida andrei lysozyme, Comp. Biochem. Physiol. 91, 187–192 (1988).Google Scholar
  41. 41.
    P. Valembois, J. Seymour, Ph. Roch, Evidence and cellular localization of an oxidative activity in the coelomic fluid of the earthworm Eisenia fetida andrei, J. Invert. Pathol. 57, 177–183 (1991).CrossRefGoogle Scholar
  42. 42.
    Ph. Roch, P. Valembois, N. Davant, M. Lassegues, Protein analysis of earthworm coelomic fluid. Isolation and biochemical characterization of the Eisenia fetida andrei factor (EFAF), Comp. Biochem. Physiol. 69, 829–836(1981).Google Scholar
  43. 43.
    A. Milochau, M. Lassegues, P. Valembois, Purification, characterization and activities of two hemolytic and antibacterial proteins from coelomic fluid of the annelid Eisenia fetida andrei, Biochem. Biophys. Acta. 1337, 123–132 (1997).CrossRefGoogle Scholar
  44. 44.
    H. Mihara, H. Sumi, T. Yoneta, H. Mizumoto, R. Ikeda, M. Seiki, M. Maruyama, A novel fibrinolytic enzyme extracted from the earthworm, Lumbricus rubellus, Jpn. J. Physiol 41, 461–472 (1991).CrossRefGoogle Scholar
  45. 45.
    H. Mihara, M. Maruyama, H. Sumi, Novel thrombolytic therapy discovered from traditional oriental medicine using the earthworm, Southeast Asia J. Trop. Med. Public Health. 23, 131–140 (1992).Google Scholar
  46. 46.
    U. Rester, I. Bode, M. Moser, M.A.A. Parry, R. Huber, E. Auerswald, Structure of the complex of the antistasin-type inhibitor bdellastasin with trypsin and modeling of the bdellastasin-microplasmin system, J. Mol. Biol. 293, 93–106 (1999).PubMedCrossRefGoogle Scholar
  47. 47.
    N. Nakajima, H. Mihara, H. Sumi, Characterization of potent fibrinolytic enzymes in earthworm, Lumbricus rubellus, Biosci. Biotechol. Biochem. 10, 1726–1730 (1993).CrossRefGoogle Scholar
  48. 48.
    N. Nakajima, K. Ishihara, M. Sugimoto, H. Sumi, K. Mikuni, H. Hamada, Chemical modification of earthworm fibrinolytic enzyme with human serum albumin fragment and characterization of the protease as a therapeutic enzyme, Biosci. Biotechnol. Biochem. 60, 293–300 (1996).PubMedCrossRefGoogle Scholar
  49. 49.
    Z.X. Zhang, F.F. Wang, Effects of crude extract of earthworm on promoting blood circulation to removing stasis, Chung Kuo Chung His I Chieh Ho Tsa Chih. 12, 741–743, 710 (1992).Google Scholar
  50. 50.
    K.M. Woo, W Yi, Y.J. Sohn, CS. Chang, M.S. Kang, D.B. Ha, C.H. Chung, Purification and characterization of a poly-L-lysine-activated serine endoprotease from Lumbricus rubellus. Comp. Biochem. Physiol. B. Biochem. Mol. Biol. 1, 71–80 (1994).Google Scholar
  51. 51.
    G.H. Ryu, S. Park, M. Kim, D.K. Han, Y.H. Kim, B. Min, Antithrombogenicity of lumbrokinase-immobilized Polyurethane, J. Biomed. Mater. Res. 28, 1069–1077 (1994).PubMedCrossRefGoogle Scholar
  52. 52.
    G.H. Ryu, Surface characteristic and properties of lumbrokinase-immobilized polyurethane, J. Biomed. Mater. Res. 29, 403–409 (1995).PubMedCrossRefGoogle Scholar
  53. 53.
    Y.S. Kim, M.K. Pyo, K.M Park, B.S. Hahn, K.Y. Yang, H.S. Yun-Choi, Dose dependency of earthworm powder on antithrombotic and fibrinolytic effects, Arch. Pharm. Res. 4, 374–377 (1998).CrossRefGoogle Scholar
  54. 54.
    Y Xiong, S.C. Yang, X.Y. Liu, L.Y. Li, B.G. Ru, Purification and determination of partial sequence of Earthworm Fibrinolytic enzyme, Chinese Biochemical Journal, 13, 292–296(1997).Google Scholar
  55. 55.
    B.D. Xing, S.M. Yin, B.G. Ru, Purification and characterization of the fibrinolytic enzyme (eFE-D) from earthworm Eisenia fetida, Acta Biochim. Biophys. Sinica. 29, 609–612 (1997).Google Scholar
  56. 56.
    J.S. Yang, B.G. Ru, Purification and Characterization of an SDS-Activated Fibrinolytic Enzyme from Eisenia fetida, Comp. Biochem. Physiol. 118B, 623–631 (1997).CrossRefGoogle Scholar
  57. 57.
    J.S. Yang, L.Y. Li, B.G. Ru, Purification of a Plasminogen Activator from Eisenia fetida, Chinese Journal of Biochemistry and Molecular Biology. 14, 156–163 (1998a).Google Scholar
  58. 58.
    J.S. Yang, L.Y Li, B.G. Ru, Characterization of a Plasminogen Activator from Eisenia fetida, Chinese Journal of Biochemistry and Molecular Biology. 14, 156–169 (1998b).Google Scholar
  59. 59.
    J.S. Yang, L.Y Li, B.G. Ru, Degradation of Benzoyl-L-argiflifle Ethyl Ester (BAEE) by a Plasminogen Activator from Eisenia fetida (e-PA), Chinese Journal of Biochemistry and Molecular Biology. 14, 412–416 (1998c).Google Scholar
  60. 60.
    J.S. Yang, L.Y Li, B.G. Ru, Degradation of N-Acetyl-L-tyrosine Ethyl Ester (ATEE) by a Plasminogen Activator from Eisenia fetida (e-PA) Chinese Journal of Biochemistry and Molecular Biology. 14, 417–421 (1998d).Google Scholar
  61. 61.
    J.S. Yang, L.Y. Li, B.G. Ru, The enzymology properties and the CD spectra of the active centers of the small subunit of a plasminogen activator from Eisenia fetida (e-PA), Chinese Journal of Biochemistry and Molecular Biology. 14, 721–725 (1998e).Google Scholar
  62. 62.
    T. Hrzenjak, M. Popovic, L. Tiska-Rudman, Fibrinolytic activity of earthworm’s extract (G-90) on lysis of fibrin clots originated from the venous blood of patients with malignant tumor, Pathol. Onco. Res. 4, 206–211 (1998).CrossRefGoogle Scholar
  63. 63.
    Ph. Roch, L. Stabili, P. Pagliara, Purification of three serine proteases from the coelomic cell of earthworms (Eisenia fetida), Comp. Biochem. Physiol. 98, 597–602 (1991).Google Scholar
  64. 64.
    C. Leipner, L. Tuckova, J. Rejneck, J. Langner, Serine proteases in coelomic fluid of annelids Eisenia fetida and Lumbricus terrestris, Comp. Biochem. Physiol. 105, 637–641 (1993).Google Scholar
  65. 65.
    A. Polanowski, and T. Wilusz, Serine proteinase inhibitors from insect hemolymph, Acta. Biochem. Polinica. 43, 445–454 (1996).Google Scholar
  66. 66.
    Ph. Roch, Protein analysis of earthworm coelomic fluid. I. Polymorphic system of the natural hemolysin of Eisenia fetida andrei. Dev. Comp. Immunol. 3, 599–608 (1979).CrossRefGoogle Scholar
  67. 67.
    Ph. Roch, C. Canicatti, P. Valembois, Interactions between earthworm hemolysins and sheep red blood cell membranes. Biochem. Biophys. Acta. 983, 193–198 (1989).PubMedCrossRefGoogle Scholar
  68. 68.
    P. Valembois, Ph. Roch, M. Lassegues, N. Davant, Bacteriostatic activity of a chloragogen cell secretion, Pedobiologia. 24, 191–195 (1982).Google Scholar
  69. 69.
    P. Valembois, Ph. Roch, M. Lassegues, Evidence of plasma clotting system in earthworms. J. Invert. Pathol. 15, 221–228 (1988).CrossRefGoogle Scholar
  70. 70.
    P. Valembois, M. Lassegues, Ph. Roch, J. Vaillier, Scanning electron-microscopic study of the involvement of coelomic cells in earthworm antibacterial defense, Cell Tissue Res. 240, 479–484 (1985).CrossRefGoogle Scholar
  71. 71.
    J.H. Cho, C.B. Park, Y.G. Yoon, S.C. Kim, Lumbricin I a novel proline-rich antimicrobial peptide from the earthworm: purification, cDNA cloning and molecular characterization. Biochim. Biophy. Acta. 1408, 67–76 (1998).CrossRefGoogle Scholar
  72. 72.
    Y Sekizawa, T. Kubo, H. Kobayashi, T. Nakajima, S. Natori, Molecular cloning of cDNA for lysenin, a novel protein in the earthworm, Eisenia foetida that causes contraction of rat vascular smooth muscle, Gene. 191, 97–102(1997).PubMedCrossRefGoogle Scholar
  73. 73.
    A. Yamaji, Y Sekizawa, K. Emoto, H. Sakuraba, K. Inoue, H. Kobayashi, M. Umeda, Lysenin, a novel sphingomyelin-specific binding protein, J Biol. Chem. 273, 300–5306, (1988).Google Scholar
  74. 74.
    N. Ohta, S. Shioda, Y Sekizawa, Y Nakai, H. Kobayashi, Sites of expression of mRNA for lysenin, a protein isolated from the coelomic fluid of the earthworm Eisenia foetida, Cell Tissue Res. 302, 263–270 (2000).CrossRefGoogle Scholar
  75. 75.
    H. Kobayashi, Y Sekizawa, M. Aizu, M. Umeda, Lethal and non-lethal responses of spermatozoa from a wide variety of vertebrates and invertebrates to lysenin, a protein from the coelomic fluid of the earthworm Eisenia foetida, J. Exp. Zool. 286, 538–549 (2000).CrossRefGoogle Scholar
  76. 76.
    H. Kobayashi, M. Ohtomi, Y Sekizawa, N. Ohta, Toxicity of coelomic fluid of the earthworm Eisenia foetida to vertebrates but not invertebrates: probable role of sphingomyelin, Comp. Biochem. Physiol. 128C, 401–411(2001).Google Scholar
  77. 77.
    A. Beschin, M. Bilej, E. Torreele, P. De Baetselier, On the existence of cytokines in invertebrates, Cell. Mol. Life Sci. 58, 801–814 (2001).PubMedCrossRefGoogle Scholar
  78. 78.
    M. Bilej, L. Brys, A. Beschin, R. Lucas, E. Vercauteren, R. Hanusova, P. De Baetselier, Identification of a cytolytic protein in the coelomic fluid of Eisenia foetida earthworms, Immunol. Lett. 45, 123–128 (1995).PubMedCrossRefGoogle Scholar
  79. 79.
    A. Beschin, M. Bilej, F. Hanssens, J. Raymakers, E. Van Dyck, H. Revets, L. Brys, J. Gomez, P. De Baetselier, M. Timermans, Identification and cloning of a glucan- and lipopolysaccharide-binding protein from Eisenia foetida earthworm involved in the activation of prophenoloxidase cascade, J. Biol. Chem. 273, 24948–24954 (1998).PubMedCrossRefGoogle Scholar
  80. 80.
    M. Bilej, P. Rossmann, M. Sinkora, R. Hanusova, A Beschin, G. Raes, P. De Baetselier, Cellular expression of the cytolytic factor in earthworms Eisenia foetida. Immunol. Lett. 60, 23–29 (1998).CrossRefGoogle Scholar
  81. 81.
    M. Bilej, P. De Baetselier, Beschin, A. Antimicrobial defense of earthworm, Folia Microbiol. 45, 283–300 (2000).CrossRefGoogle Scholar
  82. 82.
    M. Bilej, P. De Baetselier, E. Van Dijck, B. Stijlemans, A. Colige, A. Beschin, Distinct carbohydrate recognition domains of an earthworm defense molecule recognize Gram negative and Gram-positive bacteria, J. Biol. Chem. 276, 45840–45847 (2001).PubMedCrossRefGoogle Scholar
  83. 83.
    A. Beschin, M. Bilej, L. Brys, E. Torreele, R. Lucas, S. Magez, P. De Baetselier, Convergent evolution of cytokines, Nature. 400, 627–628 (1999).PubMedCrossRefGoogle Scholar
  84. 84.
    A. Bloc, R. Lucas, E. Van Dijck, M. Bilej, Y. Dunant, P. De Baetselier, A. Beschin, An invertebrate defense molecule activates membrane conductance in mammalian cells by means of its lectin-like domain, Dev. Comp. Immunol. 26, 35–43 (2002).PubMedCrossRefGoogle Scholar
  85. 85.
    E. Olivares, E. Fontt, A. Beschin, E. Van Dijck, V. Vercruysse, M. Bilej, R. Lucas, P. De Baetselier, B. Vray, Trypanosoma cruzi is lysed by coelomic cytolytic factor-1, an invertebrate analogue of TNF, and induces phenoloxidase activity in the coelomic fluid of Eisenia foetida, Dev. Comp. Immunol. 26, 27–34 (2002).CrossRefGoogle Scholar
  86. 86.
    E.L. Cooper, Phylogeny of cytotoxicity Endeavor 4, 160–165 (1981).CrossRefGoogle Scholar
  87. 87.
    E.L. Cooper, in: Immunology of Annelids, edited by V. Vetvicka et al. (CRC Press, Boca Raton 1994), pp. 1–12.Google Scholar
  88. 88.
    E.L. Cooper, in: Invertebrate Immunology, edited by B. Rinkevich and W.E.G. Müller (Springer-Verlag, Heidelberg, 1996), pp. 10–45.CrossRefGoogle Scholar
  89. 89.
    H. Nagasawa, K. Sawaki, Y. Fujii, M. Kobayashi, T. Segawa, R. Suzuki, H. Inatomi, Inhibition by lombricine from earthworm (Lumbricus terrestris) of the growth of spontaneous mammary tumors in SHN mice. Anticancer Research. 11, 1061–1064(1991).PubMedGoogle Scholar
  90. 90.
    T.M. Hrzenjak, M. Popovic, T. Bozic, M. Grdisa, D. Kobrehel, L. Tiska-Rudman, Fibrinolytic and anticoagulative activities from the earthworm Eisenia foetida, Comp. Biochem. Physiol. 119B, 825–832 (1998b).CrossRefGoogle Scholar
  91. 91.
    T. Hrzenjak, M. Hrzenjak, V. Kasuba, P. Efenberger-Marinculic, S. Levanat, A new source of biologically active compounds earthworm tissue (Eisenia foetida, Lumbricus rubellus), Comp. Biochem. Physiol. 102A, 441–447 (1992).CrossRefGoogle Scholar
  92. 92.
    M. Hrzenjak, D. Kobrehel, S. Levanat, M. Jurin, T. Hrzenjak, Mitogenicity of the earthworm’s (Eisenia foetida) insulin-like proteins, Comp. Biochem. Physiol. 104B, 723–729 (1993).Google Scholar
  93. 93.
    M. Popovic, T.M. Hrcenjak, T. Babic, J. Kos, M. Grdisa, Effect of earthworm (G-90) extract on formation and lysis of clots originated from venous blood of dogs with cardiopathies and with malignant tumors, Pathol Oncol Res. 7, 197–202 (2001).PubMedCrossRefGoogle Scholar
  94. 94.
    J.B. Xie, N. Weng, W.G. He, M.M. Yu, B.G. Ru, Antitumor activity and partial characterization of the extract from earthworm Eisenia fetida. Chinese Journal of Biochemistry and Molecular Biology, in press (2003).Google Scholar
  95. 95.
    J.B. Xie, N. Weng, W.G. He, M.M. Yu, B.G. Ru, Purification, identification and partial characterization of antitumor related Serine Protease Eisenin I. Progress in Biochemistry and Biophysics, in press (2003).Google Scholar
  96. 96.
    J.B. Xie, N. Weng, B.G. Ru, Cloning and analysis of antitumor related Serine Protease Eisenin I mRNA sequence, Progress in Biochemistry and Biophysics (in preparation).Google Scholar
  97. 97.
    P Gresele, and G. Agnelli, Novel approaches to the treatment of thrombosis, Trends in Pharmacological Sciences 23, 25–32 (2001).CrossRefGoogle Scholar
  98. 98.
    H.V. Anderson, J.T. Willerson, Thrombolysis in acute myocardial infarction, N. Engl. J. Med. 329, 703–709 (1993).PubMedCrossRefGoogle Scholar
  99. 99.
    R. Pannell, and V. Gurewich, Pro-urokinase: A study of its stability in plasma and of a mechanism for its selective fibrinolytic effect, Blood. 67, 1215–1223 (1986).PubMedGoogle Scholar
  100. 100.
    V Gurewich, R. Pannell, S. Louie, P. Kelley, R.L. Suddith, R. Greenlee, Effective and fibrin-specific clot lysis by a zymogen precursor form of urokinase (pro-urokinase): a study in vitro and in two animal species, J. Clin. Invest. 73, 1731–1739 (1984).PubMedCrossRefGoogle Scholar
  101. 101.
    R. Pannell, J. Black, V. Gurewich, The complementary modes of action of tissue-type plasminogen activator and pro-urokinase by which their synergistic effect on clot lysis may be explained, J Clin Invest. 81, 853–859 (1988).PubMedCrossRefGoogle Scholar
  102. 102.
    V. Gurewich, M. Johnstone, J.R Loza, R. Pannell, Pro-urokinase and prekallikrein are both associated with platelets: implication for the intrinsic pathway of fibrinolysis and for therapeutic thrombolysis, FEBS Lett. 318, 317–321(1993).Google Scholar
  103. 103.
    V. Gurewich, Thrombolytic agents, N. Engl. J. Med. 330, 291 (1994).PubMedCrossRefGoogle Scholar
  104. 104.
    M. Bilej, in: Immunology of annelids, edited by V. Vetvicka et al. (CRC Press, Boca Raton, 1994) pp. 167 – 200.Google Scholar
  105. 105.
    H. Mihara, Fibrinolytic enzymes extracted from the earthworm Lumbricus rubellus: a possible thrombolytic agent, Nippon Seirigaku Zasshi. 53, 231–243 (1991).PubMedGoogle Scholar
  106. 106.
    Daedo Pharmaceutical Co. Ltd., Yongshim Capsule, 1990, pp. 1–2.Google Scholar
  107. 107.
    E.W. Skowronski, R.N. Kolesnick, D.R. Green, Fas-mediated apoptosis and sphingomyelinase signal transduction: the role of ceramide as a second messenger for apoptosis, Death Different 3, 171–176 (1996).Google Scholar
  108. 108.
    S. Rowan, D.E. Fisher, Mechanisms of apoptotic cell death, Leukemia 11, 457–465 (1997).PubMedCrossRefGoogle Scholar
  109. 109.
    S. Bourteele, A. Hausser, H. Doppler, J. Horn-Muller, C. Roopke, G. Schwarzmann, K. Pfizenmaier, G. Muller, Tumor necrosis factor induces ceramide oscillations and negativity controls sphingolipid synthases by caspases in apoptotic Kym-1 cells, J. Biol. Chem. 273, 31245–31251 (1998).PubMedCrossRefGoogle Scholar
  110. 110.
    K.L. Rinehart Jr., J.B. Gloer, G.R. Wilson, R.G. Hughes Jr., L.H. Li, H.E. Renis, J.R McGovern, Antiviral and antitumor compounds from tunicates, Fed. Proc. 42, 87–90 (1983).PubMedGoogle Scholar
  111. 111.
    D.W. Montgomery, G.K. Shen, E.D. Ulrich, C.F. Zukoski, Immunomodulation by didemnins. Invertebrate marine natural products, Ann. N.Y. Acad. Sci. 712, 301–314 (1994).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2004

Authors and Affiliations

  • Edwin L. Cooper
    • 1
  • Binggen Ru
    • 2
  • Ning Weng
    • 3
  1. 1.Laboratory of Comparative Immunology, Department of Neurobiology, David Geffen School of Medicine at UCLAUniversity of CaliforniaLos AngelesUSA
  2. 2.National Laboratory of Protein Engineering, College of Life SciencePeking UniversityBeijingChina
  3. 3.Department of Biochemistry and Molecular Biology, College of Life SciencePeking UniversityBeijingChina

Personalised recommendations