Skip to main content

Novel Targets for Lung Cancer Therapy

  • Chapter
Tumors of the Chest

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Jemel A, Murray T, Samuels A, et al. Cancer statistics, 2003 CA. Cancer J Clin 2003; 53:5.

    Google Scholar 

  2. Twombly R. Failing survival advantage in crucial trial, fu ture of Iressa is in jeopardy. J Natl Cancer Inst 2005; 97:249.

    Article  PubMed  Google Scholar 

  3. Thomas P, Pang Y, Filardo EJ, Dong J. Identity of an es trogen membrane receptor coupled to a G protein in hu man breast cancer cells. Endocrinology 2005; 146:624.

    Article  PubMed  CAS  Google Scholar 

  4. Thomas SM, Grandis JR, Wentzel AL, Gooding WE, Lui VW, Siegfried JM. Gastrin-releasing peptide receptor mediates activation of the epidermal growth factor recep tor in lung cancer cells. Neoplasia 2005; 7:426.

    Article  PubMed  CAS  Google Scholar 

  5. Patel J, Bach PB, Kris MG. A contemporary epidemic. JAMA 2004; 291:1763.

    Article  PubMed  CAS  Google Scholar 

  6. Stabile LP, Davis AL, Gubish CT, et al. Human non-small cell lung tumors and cells derived from normal lung ex press both estrogen receptor alpha and beta and show biological responses to estrogen. Cancer Res 2002; 62:2141.

    PubMed  CAS  Google Scholar 

  7. Hershberger PA, Vasquez AC, Kanterewicz B, Land S, Siegfried JM, Nichols M. Regulation of endogenous gene expression in human non-small cell lung cancer cells by estrogen receptor ligands. Cancer Res 2005; 65:1598.

    Article  PubMed  CAS  Google Scholar 

  8. Moore KA, Mery CM, Jaklitsch MT, et al. Menopausal ef fects on presentation, treatment, and survival of women with non-small cell lung cancer. Ann Thorac Surg 2003; 76:1789.

    Article  PubMed  Google Scholar 

  9. Kawai H, Ishii A, Kiyotada W, et al. Estrogen receptor α and β are prognostic factors in non-small cell lung cancer. Clin Cancer Res 2005; 11:5084.

    Article  PubMed  CAS  Google Scholar 

  10. Osborne CK, Yochmowitz MG, Knight WA, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980; 46:2884.

    Article  PubMed  CAS  Google Scholar 

  11. Thorpe SM, Rose C, Rasmussen BB, Mouridsen HT, Bayer T, Keiding N. Prognostic value of steroid hormone recep tors: multivariate analysis of systemically untreated pa tients with node negative primary breast cancer. Cancer Res 1987; 47:6126.

    PubMed  CAS  Google Scholar 

  12. Stabile LP, Lyker JS, Gubish CT, Zhang W, Grandis JR, Siegfried JM. Combined targeting of the estrogen receptor and the epidermal growth factor receptor in non-small cell lung cancer shows enhanced antiproliferative effects. Cancer Res 2005; 654:1459.

    Article  Google Scholar 

  13. Hamilton A, Piccart M. The third-generation non-steroidal aromatase inhibitors: a review of their clinical benefits in the second-line hormonal treatment of advanced breast cancer. Ann Oncol 1999; 10:377.

    Article  PubMed  CAS  Google Scholar 

  14. Giudici D, Ornati G, Briatico G, Buzzetti F, Lombardi P, di Salle E. 6-Methylenandrosta-l,4-diene-3, 17-dione (FCE 24304): a new irreversible aromatase inhibitor. J Steroid Biochem 1988; 30:391.

    Article  PubMed  CAS  Google Scholar 

  15. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-l Study. J Natl Cancer Inst 1998; 90:1371.

    Article  PubMed  CAS  Google Scholar 

  16. Martel C, Meiner MH, Gagne D, Simard J, Labrie F. Wide spread tissue distribution of steroid sulfatase, 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD), 17 beta-HSD 5 alpha-reductase and aromatase activities in the rhesus monkey. Mol Cell Endocrinol 1994; 104:103.

    Article  PubMed  CAS  Google Scholar 

  17. Price T, Aitken J, Simpson ER. Relative expression of aro matase cytochrome P450 in human fetal tissues as deter mined by competitive polymerase chain reaction amplifi cation. J Clin Endocrinol Metab 1992; 744:879.

    Article  Google Scholar 

  18. Weinberg OK, Marquez-Garban DC, Chen H-W, Fishbein MC, Pietras JR. Aromatase inhibitors in human lung can cer therapy. Proc Am Assoc Cancer Res 2005; 45:4035.

    Google Scholar 

  19. Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen ther apy in postmenopausal women with primary breast can cer. N Engl J Med 2004; 350:1081.

    Article  PubMed  CAS  Google Scholar 

  20. Revankar CM, Cimino OF, Sklar LA, Arterburn JB, Prossnitz ER. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science 2005; 307:1625.

    Article  PubMed  CAS  Google Scholar 

  21. Pietras RJ, Marquez DC, Chen HW, Tsai E, Weinberg O, Fishbein M. Estrogen and growth factor receptor interac tions in human breast and non-small cell lung cancer cells. Steroids 2005; 70:372.

    Article  PubMed  CAS  Google Scholar 

  22. Rajkumar T, Gullick WJ. The type I growth factor recep tors in human breast cancer. Breast Cancer Res Treat 1994; 29:3.

    Article  PubMed  CAS  Google Scholar 

  23. Yarden Y, Sliwkowski MX. Untangling the ErbB signalling network. Nat Rev Mol Cell Biol 2001; 2:127.

    Article  PubMed  CAS  Google Scholar 

  24. Selvaggi G, Novello S, Torri V, et al. Epidermal growth factor receptor overexpression correlates with a poor prognosis in completely resected non-small-cell lung can cer. Ann Oncol 2004; 15:28.

    Article  PubMed  CAS  Google Scholar 

  25. Traynor AM, Schiller JH, Stabile LP, et al. Combination therapy with gefitinib and fulvestrant (G/F) for women with non-small cell lung cancer (NSCLC). ASCO Meeting 2005; 7224.

    Google Scholar 

  26. Okubo S, Kurebayashi J, Otsuki T, Yamamoto Y, Tanaka K, Sonoo H. Additive antitumour effect of the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (Iressa, ZD1839) and the antioestrogen fulvestrant (Faslodex, ICI182,780) in breast cancer cells. Br J Cancer 2004; 90:236.

    Article  PubMed  CAS  Google Scholar 

  27. Su JM, Hsu HK, Chang H, Un SL, Chang HC, Huang MS, Tseng HH. Expression of estrogen and progesterone re ceptors in non-small-cell lung cancer: immunohistochem-ical study. Anticancer Res 1996; 16:3803.

    PubMed  CAS  Google Scholar 

  28. Kaiser U, Hofmann J, Schilli M, et al. Steroid-hormone re ceptors in cell lines and tumor biopsies of human lung cancer. Int J Cancer 1996; 67:357.

    Article  PubMed  CAS  Google Scholar 

  29. Di Nunno L, Larsson LG, Rinehart JJ, Beissner RS. Estro gen and progesterone receptors in non-small cell lung cancer in 248 consecutive patients who underwent surgi cal resection. Arch Pathol Lab Med 2000; 124:1467.

    PubMed  Google Scholar 

  30. Ishibashi H, Suzuki T, Suzuki S, et al. Progesterone recep tor in non-small cell lung cancer: a potent prognostic fac tor and possible target for endocrine therapy. Cancer Res 2005; 65:6450.

    Article  PubMed  CAS  Google Scholar 

  31. Santen RJ, Manni A, Harvey H, Redmond C. Endocrine treatment of breast cancer in women. Endocr Rev 1990; 11:221.

    Article  PubMed  CAS  Google Scholar 

  32. Kelley RM, Baker WH. Progestational agents in the treat ment of carcinoma of the endometrium. N Engl J Med 1961; 264:216.

    Article  PubMed  CAS  Google Scholar 

  33. Kobayashi S, Mizuno T, Tobioka N, et al. Sex steroid re ceptors in diverse human tumors. Jpn J Cancer Res Gann 1982; 73:439.

    CAS  Google Scholar 

  34. Maasberg M, Rotsch M, Jaques G, Enderle-Schmidt U, Weehle R, Havemann K. Androgen receptors, androgen-dependent proliferation, and 5 alpha-reductase activity of small-cell lung cancer cell lines. Int J Cancer 1989; 434:685.

    Google Scholar 

  35. Taplin ME, Balk SP. Androgen receptor: a key molecule in the progression of prostate cancer to hormone indepen dence. J Cell Biochem 2004; 91:483.

    Article  PubMed  CAS  Google Scholar 

  36. Sonnenberg E, Meyer O, Weidner KM, Birchmeier C. Scat ter factor/hepatocyte growth factor and its receptor, the c-met tyrosine kinase, can mediate a signal exchange be tween mesenchyme and epithelia during mouse develop ment. J Cell Biol 1993; 123:223.

    Article  PubMed  CAS  Google Scholar 

  37. Schmidt C, Bladt F, Goedecke S, et al. Scatter factor/hepatocyte growth factor is essential for liver development. Nature 1995; 373:699.

    Article  PubMed  CAS  Google Scholar 

  38. Bottaro DP, Rubin JS, Faletto DL, Chan AM, Kmiecik TE, Vande Woude GF, Aaronson SA. Identification of the he-patocyte growth factor receptor as the c-met proto-oncogene product. Science 1991; 251:802.

    PubMed  CAS  Google Scholar 

  39. Park M, Dean M, Cooper CS, Schmidt M, O’Brien SJ, Blair DG, Vande Woude GF. Mechanism of met oncogene acti vation. Cell 1986; 45:895.

    Article  PubMed  CAS  Google Scholar 

  40. Schmidt L, Duh FM, Chen F, et al. Germline and somatic mutations in the tyrosine kinase domain of the MET pro-to-oncogene in papillary renal carcinomas. Nat Genet 1997; 161:68.

    Article  Google Scholar 

  41. Ma PC, Kijima T, Maulik G, et al. c-MET mutational anal ysis in small cell lung cancer: novel juxtamembrane do main mutations regulating cytoskeletal functions. Cancer Res 2003; 63:6272.

    PubMed  CAS  Google Scholar 

  42. Ma PC, Jagdeesh S, Jagadeeswaran R, Fox EA, Christensen JG, Maulik G. c-MET expression/activation, functions, and mutations in non-small cell lung cancer. Proc Am Assoc Cancer Res 2004; 44:1875.

    Google Scholar 

  43. Di Renzo MF, Olivero M, Giacomini A, et al. Overexpression and amplification of the met/HGF receptor gene dur ing the progression of colorectal cancer. Clin Cancer Res 1995; 1:147.

    PubMed  Google Scholar 

  44. Tuck AB, Park M, Sterns EE, Boag A, Elliott BE. Coexpression of hepatocyte growth factor and receptor (Met) in human breast carcinoma. Am J Pathol 1996; 148:225.

    PubMed  CAS  Google Scholar 

  45. Furukawa T, Duguid WP, Kobari M, Matsuno S, Tsao MS. Hepatocyte growth factor and Met receptor expression in human pancreatic carcinogenesis. Am J Pathol 1995; 1474:889.

    Google Scholar 

  46. Siegfried JM, Weissfeld LA, Singh-Kaw P, Weyant RJ, Testa JR, Landreneau RJ. Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer. Cancer Res 1997; 57:433.

    PubMed  CAS  Google Scholar 

  47. chimura E, Maeshima A, Nakajima T, Nakamura T. Expression of c-met/HGF receptor in human non-small cell lung carcinomas in vitro and in vivo and its prognostic significance. Jpn J Cancer Res 1996; 87:1063.

    Google Scholar 

  48. Christensen JG, Burrows J, Salgia R. c-Met as a target for human cancer and characterization of inhibitors for therapeutic intervention. Cancer Lett 2005; 225:1.

    Article  PubMed  CAS  Google Scholar 

  49. Furge KA, Zhang YW, Van de Woude GF. Met receptor tyrosine kinase: enhanced signaling through adapter proteins. Oncogene 2000; 1949:5582.

    Article  CAS  Google Scholar 

  50. Nakanishi K, Fujimoto J, Ueki T, et al. Hepatocyte growth factor promotes migration of human hepatocellular carcinoma via phosphatidylinositol 3-kinase. Clin Exp Metastasis 1999; 17:507.

    Article  PubMed  CAS  Google Scholar 

  51. Royall, Lamarche-Vane N, Lamorte L, Kaibuchi K, Park M. Activation of cdc42, rae, PAK, and rho-kinase in re sponse to hepatocyte growth factor differentially regulates epithelial cell colony spreading and dissociation. Mol Biol Cell 2000; 11:1709.

    Google Scholar 

  52. Kodama A, Takaishi K, Nakano K, Nishioka H, Takai Y. Involvement of Cdc42 small G protein in cell-cell adhesion, migration and morphology of MOCK cells. Oncogene 1999; 18:3996.

    Article  PubMed  CAS  Google Scholar 

  53. Ishizawa K, Kubo H, Yamada M, et al. Hepatocyte growth factor induces angiogenesis in injured lungs through mobilizing endothelial progenitor cells. Biochem Biophys Res Commun 2004; 324:276.

    Article  PubMed  CAS  Google Scholar 

  54. Wislez M, Rabbe N, Marchal J, et al. Hepatocyte growth factor production by neutrophils infiltrating bronchioloalveolar subtype pulmonary adenocarcinoma: role in tumor progression and death. Cancer Res 2003; 636:1405.

    Google Scholar 

  55. Dong G, Lee TL, Yeh NT, Geoghegan J, Van Waes C, Chen Z. Metastatic squamous cell carcinoma cells that overexpress c-Met exhibit enhanced angiogenesis factor expression, scattering and metastasis in response to hepatocyte growth factor. Oncogene 2004; 23:6199.

    Article  PubMed  CAS  Google Scholar 

  56. Christensen JG, Schreck R, Burrows J, et al. A selective small molecule inhibitor of c-Met kinase inhibits c-Met-dependent phenotypes in vitro and exhibits cytoreductive antitumor activity in vivo. Cancer Res 2003; 63:7345.

    PubMed  CAS  Google Scholar 

  57. Ma PC, Schaefer E, Christensen JG, Salgia R. Selective small molecule c-MET inhibitor, PHA665752, cooperates with rapamycin. Clin Cancer Res 2005; 11:3212.

    Google Scholar 

  58. Abounader R, Ranganathan S, Lal B, Fielding K, Book A, Dietz H, Burger P, Laterra J. Reversion of human glioblastoma malignancy by Ul small nuclear RNA/ribozyme targeting of scatter factor/hepatocyte growth factor and c-met expression. J Natl Cancer Inst 1999; 91:1548.

    Article  PubMed  CAS  Google Scholar 

  59. Abounader R, Bachchu L, Luddy C, Koe G, Davidson B, Rosen EM, Laterra J. In vivo targeting of SF/HGF and c-met expression via UlsnRNA/ribozymes inhibits glioma growth and angiogenesis and promotes apoptosis. FASEB J 2002; 16:108.

    PubMed  CAS  Google Scholar 

  60. Kaplan O, Firon M, Vivi A, Navon G, Tsarfaty I. HGF/SF activates glycolysis and oxidative phosphorylation in DA3 murine mammary cancer cells. Neoplasia 2000; 24:365.

    Article  CAS  Google Scholar 

  61. Stabile LP, Lyker JS, Huang L, Siegfried JM. Inhibition of human non-small cell lung tumors by a c-Met antisense/U6 expression plasmid strategy. Gene Ther 2004; 11:325.

    Article  PubMed  CAS  Google Scholar 

  62. Webb CP, Taylor GA, Jeffers M, Fiscella M, Oskarsson M, Resau JH, Van de Woude GF. Evidence for a role of Met-HGF/SF during Ras-mediated tumorigenesis/metastasis. Oncogene 1998; 17:2019.

    Article  PubMed  CAS  Google Scholar 

  63. Michieli P, Mazzone M, Basilico C, Cavassa S, Sottile A, Naldini L, Comoglio PM. Targeting the tumor and its microenvironment by a dual-function decoy Met receptor. Cancer Cell 2004; 6:61.

    Article  PubMed  CAS  Google Scholar 

  64. Bardelli A, Longati P, Gramaglia D, et al. Uncoupling signal transducers from oncogenic MET mutants abrogates cell transformation and inhibits invasive growth. Proc Natl Acad Sci U S A 1998; 95:14379.

    Article  PubMed  CAS  Google Scholar 

  65. Atabey N, Gao Y, Yao ZJ, et al. Potent blockade of hepatocyte growth factor-stimulated cell motility, matrix invasion and branching morphogenesis by antagonists of Grb2 Src homology 2 domain interactions. J Biol Chem 2001; 276:14308.

    PubMed  CAS  Google Scholar 

  66. Cao B, Su Y, Oskarsson M, et al. Neutralizing monoclonal antibodies to hepatocyte growth factor/scatter factor (HGF/SF) display antitumor activity in animal models. Proc Natl Acad Sci U S A 2001; 98:7443.

    Article  PubMed  CAS  Google Scholar 

  67. Zheng ZAC, Moffat B, Schwall R. A chimeric Fab antibody serves as an antagonist to the HGF/SF receptor c-Met. Proc Am Assoc Cancer Res 2003; 43:5717.

    Google Scholar 

  68. Morton PA, Joy WD, Bobo CP, Arbuckle A, Evans ML, Huynh MS. In vitro and in vivo activity of fully human monoclonal antibody antagonists to c-Met protein tyrosine kinase. Proc Am Assoc Cancer Res 2003; 43:5604.

    Google Scholar 

  69. Date K, Matsumoto K, Shimura H, Tanaka M, Nakamura I. HGF/NK4 is a specific antagonist for pleiotrophic actions of hepatocyte growth factor. FEBS Lett 1997; 4201:1.

    Article  Google Scholar 

  70. Jiang WG, Hiscox SE, Parr C, Martin TA, Matsumoto K, Nakamura T, Mansel RE. Antagonistic effect of NK4, a novel hepatocyte growth factor variant, on in vitro angiogenesis of human vascular endothelial cells. Clin Cancer Res 1999; 5:3695.

    PubMed  CAS  Google Scholar 

  71. Parr C, Hiscox S, Nakamura T, Matsumoto K, Jiang WG. NK4, a new HGF/SF variant, is an antagonist to the influence of HGF/SF on the motility and invasion of colon cancer cells. Int J Cancer 2000; 854:563.

    Article  Google Scholar 

  72. Hiscox S, Parr C, Nakamura T, Matsumoto K, Mansel RE, Jiang WG. Inhibition of HGF/SF-induced breast cancer cell motility and invasion by the HGF/SF variant, NK4. Breast Cancer Res Treat 2000; 59:245.

    Article  PubMed  CAS  Google Scholar 

  73. Chan AM, Rubin JS, Bottaro DP, Hirschfield DW, Chedid M, Aaronson SA. Identification of a competitive HGF antagonist encoded by an alternative transcript. Science 1991; 254:1382.

    PubMed  CAS  Google Scholar 

  74. Kuba K, Matsumoto K, Date K, Shimura H, Tanaka M, Nakamura T. HGF/NK4, a four-kringle antagonist of hepatocyte growth factor, is an angiogenesis inhibitor that suppresses tumor growth and metastasis in mice. Cancer Res 2000; 60:6737.

    PubMed  CAS  Google Scholar 

  75. Maemondo M, Narumi K, Saijo Y, et al. Targeting angiogenesis and HGF function using an adenoviral vector expressing the HGF antagonist NK4 for cancer therapy. Mol Ther 2002; 52:177.

    Article  CAS  Google Scholar 

  76. Yee CJ, DeFrances MC, Bell A, Bowen W, Petersen B, Michalopoulos GK, Zarnegar R. Expression and characterization of biologically active human hepatocyte growth factor (HGF) by insect cells infected with HGF-recombinant baculovirus. Biochemistry 1993; 32:7922.

    Article  PubMed  CAS  Google Scholar 

  77. Cuttitta F, Carney DN, Mulshine J, Moody TW, Fedorko J, Fischler A, Minna JD. Bombesin-like peptides can function as autocrine growth factors in human small-cell lung cancer. Nature 1985; 316:823.

    Article  PubMed  CAS  Google Scholar 

  78. Lango MN, Dyer KF, Lui VWY, Gooding WE, Gubish C, Siegfried JM, Grandis JR. Gastrin-releasing peptide receptor-mediated autocrine growth in squamous cell carcinoma of the head and neck. J Natl Cancer Inst 2002; 94:375.

    PubMed  CAS  Google Scholar 

  79. Siegfried JM, Krishnamachary Gaither-Davis A, Gubish C, Hunt JD, Shriver SP. Evidence to autocrine actions of neuromedin B and gastrin-releasing peptide in non-small cell lung cancer. Pulm Pharmacol Ther 1999; 12:291.

    Article  PubMed  CAS  Google Scholar 

  80. Schally AV, Comaru-Schally AM, Nagy A, et al. Hypothalamic hormones and cancer. Front Neuroendocrinol 201; 22:248.

    Google Scholar 

  81. Emanuel RL, Torday JS, Mu Q, Asoknanthan N, Sikorski KA, Sunday ME. Bombesin-like peptides and receptors in normal fetal baboon lung: roles in lung growth and maturation. Am J Physiol 1999; 277:L1003.

    PubMed  CAS  Google Scholar 

  82. Martinez A, Zudaire E, Julian M, Moody TW, Cuttitta F. Gastrin-releasing peptide (GRP) induces angiogenesis and the specific GRP blocker 77427 inhibits tumor growth in vitro and in vivo. Oncogene 2005; 24:4106.

    PubMed  CAS  Google Scholar 

  83. Chadhry A, Carrasquillo JA, Avis IL, et al. Phase I and imaging trial of a monoclonal antibody directed against gastrin-releasing peptide in patients with lung cancer. Clin Cancer Res 1999; 5:3385.

    Google Scholar 

  84. Radulovic S, Cai RZ, Serfozo P, et al. Biological effects and receptor binding affinities of new pseudononapeptide bombesin/GRP receptor antagonists with N-terminal D-Trp or DTpi. Int J Pept Protein Res 1991; 38:593.

    Article  PubMed  CAS  Google Scholar 

  85. Nagy A, Armatis P, Cai RZ, Szepeshazi K, Halmos G, Schally AV. Design, synthesis, and in vitro evaluation of cytotoxic analogs of bombesin-like peptides containing doxorubicin or its intensely potent derivative, 2-pyrroli-nodoxorubicin. Proc Natl Acad Sci U S A 1997; 94:652.

    Article  PubMed  CAS  Google Scholar 

  86. Engel JB, Keller G, Schally AV, Halmos G, Hammann B, Nagy A. Effective inhibition of the experimental human ovarian cancers with a targeted cytotoxic bombesin analogue AN-215. Clin Cancer Res 2005; 11:2408.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer Berlin Heidelberg

About this chapter

Cite this chapter

Siegfried, J.M., Stabile, L.P. (2006). Novel Targets for Lung Cancer Therapy. In: Syrigos, K.N., Nutting, C.M., Roussos, C. (eds) Tumors of the Chest. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-31040-1_35

Download citation

  • DOI: https://doi.org/10.1007/3-540-31040-1_35

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-31039-6

  • Online ISBN: 978-3-540-31040-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics