Donald School Journal of Ultrasound in Obstetrics and Gynecology

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VOLUME 2 , ISSUE 4 ( October-December, 2008 ) > List of Articles

RESEARCH ARTICLE

Ultrasound Imaging in Animal Models of Human Disease—Is it a Step Toward Early Diagnosis in Humans?

Jacques S Abramowicz, Animesh Barua, Pincas Bitterman, Janice M Bahr, Eyal Sheiner, Judith L Luborsky

Keywords : Ovarian cancer,animal models,chicken,ultrasound,Doppler,contrast agents

Citation Information : Abramowicz JS, Barua A, Bitterman P, Bahr JM, Sheiner E, Luborsky JL. Ultrasound Imaging in Animal Models of Human Disease—Is it a Step Toward Early Diagnosis in Humans?. Donald School J Ultrasound Obstet Gynecol 2008; 2 (4):58-64.

DOI: 10.5005/jp-journals-10009-1078

License: CC BY-NC 4.0

Published Online: 01-12-2009

Copyright Statement:  Copyright © 2008; The Author(s).


Abstract

Despite extensive research, cancer of the ovaries remains a major medical problem. The main reason is delay in diagnosis and hence, poor prognosis. This is due to issues in screening and a lack of specific symptoms in early disease. Yearly ultrasound examination and measurement of serum CA125 remain the recommended method despite less than ideal results. Animal research plays a major role in medical research, especially in cancer. Many publications describe the use of ultrasound in cancer research in a large variety of animals. Bmode, spectral and color Doppler have been employed and, more recently, ultrasound contrast agents, both for diagnostic and therapeutic purposes. We have demonstrated that ultrasound can be used to detect early ovarian cancer in the egg-laying chicken. The major advantage is that chickens develop spontaneous ovarian cancer, with a tumor histology that is identical to humans. Furthermore, chickens with ovarian tumors have serum anti-tumor antibodies similar to humans. In addition, the first sign that the egg-laying chicken is going to develop cancer is that it stops laying eggs prematurely.* Thus, a strong biological sign exists to categorize the chicken in a very high risk group, allowing sequential examinations at very close intervals. We have also shown that ultrasound contrast agents may be used for visualization of ovarian vascularity, a step, we hope, in the development of better methods for screening and early diagnosis.


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  1. A quantitative analysis of the costs and benefits of prostate cancer screening. Prostate Cancer Prostatic Dis 2001;4(3):138-45.
  2. Cancer statistics, 2008. CA Cancer J Clin 2008; 58(2):71-96.
  3. Ovarian cancer screening: a look at the evidence. Clin J Oncol Nurs 2006;10(1):77-81.
  4. Early detection of ovarian cancer. Dis Markers 2007;23(5-6):397-410.
  5. Pathogenesis of ovarian cancer: lessons from morphology and molecular biology and their clinical implications. Int J Gynecol Pathol 2008;27(2):151-60.
  6. Malignancies following bilateral salpingooophorectomy (BSO) Eur J Surg Oncol 2006;32(10):1231-34.
  7. Serum CA125 level before the development of ovarian cancer. Int J Gynaecol Obstet 2007;99(2):95-99.
  8. Screening in ovarian cancer. Am J Obstet Gynecol 1991;165(1):7-10.
  9. Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. Bjog 2007;114(12): 1500-09.
  10. Defining women at high risk of ovarian cancer. Cancer Res 2007;67(6):2902; author reply 2902-03.
  11. Ovarian cancer screening. Aust Fam Physician 2007;36(3):126-28.
  12. Prevention and early detection of ovarian cancer: mission impossible? Recent Results Cancer Res 2007; 174:91-100.
  13. Multianalyte profiling of serum antigens and autoimmune and infectious disease molecules to identify biomarkers dysregulated in epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 2008;17(10):2872-81.
  14. Diagnostic Markers for Ovarian Cancer Screening: Not Ready for Routine Clinical Use. Clin Cancer Res 2008.
  15. CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer. Gynecol Oncol 2006;100(1):20-26.
  16. Biomarkers of ovarian tumours. Eur J Cancer 2004;40(17):2604-12.
  17. Lysophosphatidic acid as a potential biomarker for ovarian and other gynecologic cancers. Jama 1998;280(8):719-23.
  18. Lysophospholipids are potential biomarkers of ovarian cancer. Cancer Epidemiol Biomarkers Prev 2004;13(7):1185-91.
  19. Protein expression levels of carcinoembryonic antigen (CEA) in Danish ovarian cancer patients: from the Danish ‘MALOVA'ovarian cancer study. Pathology 2008;40(5):487-92.
  20. Elevated serum alkaline phosphatase may enable early diagnosis of ovarian cancer. Eur J Obstet Gynecol Reprod Biol 1999;86(1):69-71.
  21. CA125 and placental alkaline phosphatase as serum tumor markers in epithelial ovarian carcinoma. Tumour Biol 1992;13(3):168-74.
  22. Systematic evaluation of candidate blood markers for detecting ovarian cancer. PLoS ONE 2008;3(7):e2633.
  23. Combining multiple serum tumor markers improves detection of stage I epithelial ovarian cancer. Gynecol Oncol 2007;107(3):526-31.
  24. Evaluation of biomarker panels for early stage ovarian cancer detection and monitoring for disease recurrence. Gynecol Oncol 2008;110(3):374-82.
  25. Prognostic significance of extracellular matrix metalloproteinase inducer and matrix metalloproteinase 2 in epithelial ovarian cancer. Tumour Biol 2007;28(5):280-89.
  26. Human tissue kallikrein 7, a novel biomarker for advanced ovarian carcinoma using a novel in situ quantitative method of protein expression. Ann Oncol 2008;19(7):1271-77.
  27. Serum mesothelin in epithelial ovarian carcinoma: a new screening marker and prognostic factor. Anticancer Res 2006;26(6C):4721-28.
  28. Osteopontin as a potential diagnostic biomarker for ovarian cancer. Jama 2002;287(13):1671-79.
  29. Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology. J Natl Cancer Inst 2001;93(19):1458-64.
  30. Evaluation of recombinant human interleukin-12 in patients with recurrent or refractory ovarian cancer: a gynecologic oncology group study. Gynecol Oncol 2001;82(1): 7-10.
  31. IL-6 production in ovarian carcinoma is associated with histiotype and biological characteristics of the tumour and influences local immunity. Br J Cancer 2000;82(3):621-28.
  32. Circulating IL-8 and anti-IL-8 autoantibody in patients with ovarian cancer. Gynecol Oncol 2006;102(2): 244-51.
  33. Expression of IL-10 in patients with ovarian carcinoma. Anticancer Res 2006;26(2C):1715-18.
  34. Markers of angiogenesis in ovarian cancer. Dis Markers 2007;23(5-6):419-31.
  35. Early Detection of Ovarian Cancer: New Technologies in Pursuit of a Disease that is neither Common nor Rare. Trans Am Clin Climatol Assoc 2004;115:233-48.
  36. Protein expression profiling in human lung, breast, bladder, renal, colorectal and ovarian cancers. J Chromatogr B Analyt Technol Biomed Life Sci 2003;787(1):207-22.
  37. Ovarian cancer in the proteomics era. Int J Gynecol Cancer 2008;18 Suppl 1:1-6.
  38. 3rd, Clinical potential of proteomics in the diagnosis of ovarian cancer. Expert Rev Mol Diagn 2002;2(4):312-20.
  39. Epigenetic markers of ovarian cancer. Adv Exp Med Biol 2008;622:35-51.
  40. Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets. Int J Gynecol Cancer 2005;15Suppl 3:266-73.
  41. The search for predictive patterns in ovarian cancer: proteomics meets bioinformatics. Cancer Cell 2002;1(2):111-12.
  42. Predicting the clinical behavior of ovarian cancer from gene expression profiles. Int J Gynecol Cancer 2006;16Suppl 1:147-51.
  43. Comparative proteome analysis of human epithelial ovarian cancer. Proteome Sci 2007;5:16.
  44. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002;359(9306):572-77.
  45. Anti-tumor antibodies in ovarian cancer. Am J Reprod Immunol 2005;54(2):55-62.
  46. Anti-tumor and anti-ovarian autoantibodies in women with ovarian cancer. Am J Reprod Immunol 2007; 57(4):243-49.
  47. Ultrasonographic contrast media: has the time come in obstetrics and gynecology? J Ultrasound Med 2005; 24(4):517-31.
  48. Assessment of microvascular perfusion changes in a rat breast tumor model using SonoVue to monitor the effects of different anti-angiogenic therapies. Acad Radiol 2005;12 Suppl 1:S28-33.
  49. Contrast-enhanced sonography of tumor neovascularity in a rabbit model. Ultrasound Med Biol 1998; 24(4):495-501.
  50. Contrast-enhanced ultrasound for examining tumor biology. Cancer Imaging 2006;6:148-52.
  51. Contrast-enhanced ultrasonographic imaging diagnosis on assessment of vascularity in liver metastatic lesions. World J Gastroenterol 2005;11(23):3610-13.
  52. Imaging tumor angiogenesis with contrast ultrasound and microbubbles targeted to alpha(v)beta3. Circulation 2003;108(3):336-41.
  53. Quantification of tumor vascularity with contrast-enhanced sonography: correlation with magnetic resonance imaging and fluorodeoxyglucose autoradiography in an implanted tumor. J Ultrasound Med 2004;23(1):37-41.
  54. Contrast-enhanced transrectal ultrasonography of a novel canine prostate cancer model. J Ultrasound Med 2002;21(9):1003-13.
  55. Assessment of angiogenesis: implications for ultrasound imaging. Ultrasonics 2004;42(1-9):325-30.
  56. B-mode enhancement of the liver with microbubble contrast agent: a blinded study in rabbits with VX2 tumors. Acad Radiol 2001;8(8):734-40.
  57. Tumor vascularity: evaluation in a murine model with contrast-enhanced color Doppler US effect of angiogenesis inhibitors. Radiology 2002;222(2):460-67.
  58. A multivessel model describing replenishment kinetics of ultrasound contrast agent for quantification of tissue perfusion. Ultrasound Med Biol 2003;29(10):1421-30.
  59. Sensitive noninvasive monitoring of tumor perfusion during antiangiogenic therapy by intermittent bolus-contrast power Doppler sonography. Cancer Res 2003;63(23):8264-70.
  60. Time-intensity-based quantification of vascularity with single-level dynamic contrast-enhanced ultrasonography: a pilot animal study. J Ultrasound Med 2005;24(7):975-83.
  61. Nanoparticles as image enhancing agents for ultrasonography. Phys Med Biol 2006;51(9):2179-89.
  62. Anti-angiogenic gene therapy for hepatocellular carcinoma mediated by microbubble-enhanced ultrasound exposure: an in vivo experimental study. J Drug Target 2008. 16(5):389-95.
  63. Microultrasound molecular imaging of vascular endothelial growth factor receptor 2 in a mouse model of tumor angiogenesis. Mol Imaging 2007;6(5):289-96.
  64. Dose-response relationship of ultrasound contrast agent in an in vivo murine melanoma model. Cancer Imaging 2007;7:216-23.
  65. Quantitative assessment of tumor enhancement by ultrastable lipid-coated microbubbles as a sonographic contrast agent. Invest Radiol 1992;27(1):29-34.
  66. Characterization of tumor imaging with microbubble-based ultrasound contrast agent, sonazoid, in rabbit liver. Biol Pharm Bull 2005;28(6):972-77.
  67. Ultrasonic imaging of tumor angiogenesis using contrast microbubbles targeted via the tumor-binding peptide arginine-arginine-leucine. Cancer Res 2005;65(2):533-39.
  68. US imaging of tumor angiogenesis with microbubbles targeted to vascular endothelial growth factor receptor type 2 in mice. Radiology 2008;246(2):508-18.
  69. Correlation between estimates of tumor perfusion from microbubble contrast-enhanced sonography and dynamic contrast-enhanced magnetic resonance imaging. J Ultrasound Med 2006;25(4):487-97.
  70. Ultrasonic assessment of hepatic blood flow as a marker of mouse hepatocarcinoma. Ultrasound Med Biol 2007; 33(4):561-70.
  71. Development and growth pattern of small hepatocellular carcinomas in woodchucks—analysis of an animal model of human hepatocellular carcinoma by ultrasonography. Jikken Dobutsu 1991;40(4):545-48.
  72. Rodent models for ovarian cancer research. Int J Gynecol Cancer 2003;13(4):405-12.
  73. Animal models of ovarian cancer. Reprod Biol Endocrinol 2003;1:67.
  74. 3D thoracoscopic ultrasound volume measurement validation in an ex vivo and in vivo porcine model of lung tumours. Phys Med Biol 2007;52(1):91-106.
  75. Ultrasonography in the study of hepatocellular carcinoma in woodchucks chronically infected with WHV. Lab Anim 2003;37(3):233-40.
  76. Ultrasound detection of spontaneous hepatocellular carcinomas in X/myc bitransgenic mice. Liver Int 2004; 24(6):651-57.
  77. Vascularity of hepatic VX2 tumors of rabbits: assessment with conventional power Doppler US and contrast enhanced harmonic power Doppler US. World J Gastroenterol 2003;9(2):258-61.
  78. Three-dimensional high-frequency ultrasound imaging for longitudinal evaluation of liver metastases in preclinical models. Cancer Res 2005;65(12):5231-37.
  79. Sequence of an exon of tumour suppressor p53 gene—a comparative study in domestic animals: mutation in a feline solid mammary carcinoma. Br Vet J 1995;151(3):325-29.
  80. In vivo quantitation of tumour vascularisation assessed by Doppler sonography in rat mammary tumours. Ultrasound Med Biol 2002;28(4):431-37.
  81. Three-dimensional ultrasound biomicroscopy for xenograft growth analysis. Ultrasound Med Biol 2005; 31(6):865-70.
  82. Detecting vascular changes in tumour xenografts using micro-ultrasound and micro-ct following treatment with VEGFR-2 blocking antibodies. Ultrasound Med Biol 2007;33(8):1259-68.
  83. A new three-dimensional ultrasound microimaging technology for preclinical studies using a transgenic prostate cancer mouse model. Cancer Res 2005; 65(14):6337-45.
  84. Functional imaging of angiogenesis in an orthotopic model of pancreatic cancer. J Cell Biochem 2003;90(3):492-501.
  85. Ovarian tumours in laboratory and domestic animals. Curr Top Pathol 1989;78:1-10.
  86. A mouse model repository for cancer biomarker discovery. J Proteome Res 2008;7(8):3613-38.
  87. Ultrasound biomicroscopy permits in vivo characterization of zebrafish liver tumors. Nat Methods 2007;4(7):551-53.
  88. Some unusual gonadal tumours of the fowl. Br J Cancer 1951;5(1):69-82.
  89. Ovarian tumors of the hen. Environ Health Perspect 1987;73:35-51.
  90. Dietary aspirin decreases the stage of ovarian cancer in the hen. Gynecol Oncol 2008.
  91. Immunohistochemical expression of molecular markers in an avian model: a potential model for preclinical evaluation of agents for ovarian cancer chemoprevention. Gynecol Oncol 2001;81(3):373-79.
  92. Ovarian tumor expression of an oviductal protein in the hen: a model for human serous ovarian adenocarcinoma. Gynecol Oncol 2004;95(3): 530-33.
  93. Use of ultrasonography to characterize ovarian status in chicken. Poult Sci 2002;81(6):892-95.
  94. Detection of ovarian tumors in chicken by sonography: a step toward early diagnosis in humans? J Ultrasound Med 2007;26(7):909-19.
  95. Anti-ovarian and anti-tumor antibodies in women with ovarian cancer. Am J Reprod Immunol 2007;57:243-49.
  96. Prevalence of anti-tumor antibodies in the laying hen model of human ovarian cancer. International Journal of Gynecological Cancer 2008 (in press).
  97. The promise and perils of ‘targeted therapy’ of advanced ovarian cancer. Oncology 2008;74(1-2):1-6.
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