Gynecologic and Obstetric Investigation

Original Article

Free Access

Towards Fibroid Gene Therapy: Adenovirus-Mediated Delivery of Herpes Simplex Virus 1 Thymidine Kinase Gene/Ganciclovir Shrinks Uterine Leiomyoma in the Eker Rat Model

Hassan M.a, d · Zhang D.a, c · Salama S.a, d · Hamada F.d · Arafa H.d · Fouad H.a · Walker C.b · Al-Hendy A.a, c

Author affiliations

aDepartment of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, Tex., bM.D. Anderson Cancer Center, University of Texas, Smithville, Tex., and cDepartment of Obstetrics and Gynecology, Meharry Medical College, Nashville, Tenn., USA; dDepartment of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

Corresponding Author

Prof. Ayman Al-Hendy, MD, PhD

1005 Dr. D.B. Todd Jr. Blvd., George Hubbard Hospital

5th Floor, Room 5131C

Nashville, TN 37208 (USA)

Tel. +1 615 963 3148, Fax +1 615 963 3125, E-Mail ahendy@MMC.edu

Keywords: LeiomyomaGene therapyHSV1TK/GCVEker rat

Related Articles for ""
Gynecol Obstet Invest 2009;68:19–32
https://doi.org/10.1159/000209675

Abstract

Background/Aims: The objective of this study was to assess in vivo gene therapy of uterine leiomyomas in the Eker rat model using adenovirus (Ad)-mediated delivery of herpes simplex virus 1 thymidine kinase gene (HSV1TK) followed by ganciclovir (GCV) treatment. Methods: We randomized 27 female Eker rats with MRI-confirmed uterine leiomyomas to a single treatment with direct intra-tumor injection of Ad-HSV1TK/GCV, Ad-LacZ/GCV, or medium alone. Samples were collected from tumors, other body organs, and blood at 10, 20, and 30 days after treatment to assess the safety and efficacy of the treatment. Results: Ad-HSV1TK/GCV treatment significantly decreased uterine fibroid volume by 75 ± 16, 58.7 ± 6.3, and 67.5 ± 27.5%, of the pretreatment volume at days 10, 20, and 30, respectively. Ad-HSV1TK/GCV increased caspase-3 activity, Bax expression, and TUNEL apoptosis marker, and it decreased cyclin D1, PCNA, Bcl2, and PARP protein expressions. Ad transfection induced local CD4+ and CD8+ infiltration and serum anti-Ad antibodies. Additionally, Ad transfection was tumor-localized and safe to non-target tissues. Conclusion: These studies demonstrate a marked efficiency and high safety for the Ad-HSV1TK/GCV therapeutic approach in the context of Eker rat uterine leiomyomas and provide essential preclinical data for the development of Ad-HSV1TK/GCV gene therapy for uterine fibroids.

© 2009 S. Karger AG, Basel



Related Articles:

References

  1. Stewart EA: Uterine fibroids. Lancet 2001;357:293–298.
    External Resources
  2. Farhi J, Ashkenazi J, Feldberg D, Dicker D, Orvieto R, Ben Rafael Z: Effect of uterine leiomyomata on the results of in-vitro fertilization treatment. Hum Reprod 1995;10:2576–2578.
    External Resources
  3. Hart R, Khalaf Y, Yeong CT, Seed P, Taylor A, Braude P: A prospective controlled study of the effect of intramural uterine fibroids on the outcome of assisted conception. Hum Reprod 2001;16:2411–2417.
    External Resources
  4. Surrey ES, Lietz AK, Schoolcraft WB: Impact of intramural leiomyomata in patients with a normal endometrial cavity on in vitro fertilization-embryo transfer cycle outcome. Fertil Steril 2001;75:405–410.
    External Resources
  5. Vilos GA: Uterine fibroids: relationships to reproduction. Minerva Ginecol 2003;55:417–423.
    External Resources
  6. Walker CL, Stewart EA: Uterine fibroids: the elephant in the room. Science 2005;308:1589–1592.
    External Resources
  7. Lefebvre G, Allaire C, Jeffrey J, Vilos GA, Arneja J, Birch C, Fortier M; Clinical Practice Gynaecology Committee and Executive Committee and Council, Society of Obstetricians and Gynaecologists of Canada: SOGC clinical guidelines. Hysterectomy. J Obstet Gynaecol Can 2002;24:37–76.
    External Resources
  8. Andreyko JL, Marshall LA, Dumesic DA, Jaffe RB: Therapeutic uses of gonadotropin-releasing hormone analogs. Obstet Gynecol Surv 1987;42:1–21.
    External Resources
  9. Al Hendy A, Salama S: Gene therapy and uterine leiomyoma: a review. Hum Reprod Update 2006;16:385–400.
    External Resources
  10. Vassaux G, Martin-Duque P: Use of suicide genes for cancer gene therapy: study of the different approaches. Expert Opin Biol Ther 2004;4:519–530.
    External Resources
  11. Tasciotti E, Zoppe M, Giacca M: Transcellular transfer of active HSV-1 thymidine kinase mediated by an 11-amino-acid peptide from HIV-1 Tat. Cancer Gene Ther 2003;10:64–74.
    External Resources
  12. Reid R, Mar EC, Huang ES, Topal MD: Insertion and extension of acyclic, dideoxy, and ara nucleotides by herpesviridae, human-alpha and human-beta polymerases: a unique inhibition mechanism for 9-(1,3-dihydroxy-2-propoxymethyl)guanine triphosphate. J Biol Chem 1988;263:3898–3904.
    External Resources
  13. Robe PA, Princen F, Martin D, Malgrange B, Stevenaert A, Moonen G, Gielen J, Merville MP, Bours V: Pharmacological modulation of the bystander effect in the herpes simplex virus thymidine kinase/ganciclovir gene therapy system: effects of dibutyryl adenosine 3′,5′-cyclic monophosphate, alpha-glycyrrhetinic acid, and cytosine arabinoside. Biochem Pharmacol 2000;60:241–249.
    External Resources
  14. Palu G, Cavaggioni A, Calvi P, Franchin E, Pizzato M, Boschetto R, Parolin C, Chilosi M, Ferrini S, Zanusso A, Colombo F: Gene therapy of glioblastoma multiforme via combined expression of suicide and cytokine genes: a pilot study in humans. Gene Ther 1999;6:330–337.
    External Resources
  15. Rubsam LZ, Boucher PD, Murphy PJ, KuKuruga M, Shewach DS: Cytotoxicity and accumulation of ganciclovir triphosphate in bystander cells cocultured with herpes simplex virus type 1 thymidine kinase-expressing human glioblastoma cells. Cancer Res 1999;59:669–675.
    External Resources
  16. Salama S, Kamel M, Christman G, Wang H, Al-Hendy A: Gene therapy of uterine fibroids: adenovirus-mediated herpes simplex virus thymidine kinase/ganciclovir treatment inhibits growth of human and rat leiomyoma cells. Gynecol Obstet Invest 2007;63:61–70.
    External Resources
  17. Freeman SM, Abboud CN, Whartenby KA, Packman CH, Koeplin DS, Moolten FL, Abraham GN: The ‘bystander effect’: tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res 1993;53:5274–5283.
    External Resources
  18. Smythe WR, Hwang HC, Elshami AA, Amin KM, Eck SL, Davidson BL, Wilson JM, Kaiser LR, Albelda SM: Treatment of experimental human mesothelioma using adenovirus transfer of the herpes simplex thymidine kinase gene. Ann Surg 1995;222:78–86.
    External Resources
  19. Everitt JI, Wolf DC, Howe SR, Goldsworthy TL, Walker C: Rodent model of reproductive tract leiomyomata. Clinical and pathological features. Am J Pathol 1995;146:1556–1567.
    External Resources
  20. Houston KD, Hunter DS, Hodges LC, Walker CL: Uterine leiomyomas: mechanisms of tumorigenesis. Toxicol Pathol 2001;29:100–104.
    External Resources
  21. Cook JD, Walker CL: The Eker rat: establishing a genetic paradigm linking renal cell carcinoma and uterine leiomyoma. Curr Mol Med 2004;4:813–824.
    External Resources
  22. Al-Hendy A, Lee EJ, Wang HQ, Copland JA: Gene therapy of uterine leiomyomas: adenovirus-mediated expression of dominant negative estrogen receptor inhibits tumor growth in nude mice. Am J Obstet Gynecol 2004;191:1621–1631.
    External Resources
  23. Chen SH, Shine HD, Goodman JC, Grossman RG, Woo SL: Gene therapy for brain tumors: regression of experimental gliomas by adenovirus-mediated gene transfer in vivo. Proc Natl Acad Sci USA 1994;91:3054–3057.
    External Resources
  24. Al-Hendy A, Magliocco AM, Al Tweigeri T, Braileanu G, Crellin N, Li H, Strong T, Curiel D, Chedrese PJ: Ovarian cancer gene therapy: repeated treatment with thymidine kinase in an adenovirus vector and ganciclovir improves survival in a novel immunocompetent murine model. Am J Obstet Gynecol 2000;182:553–559.
    External Resources
  25. Quast MJ, Neumeister H, Ezell EL, Budelmann BU: MR microscopy of cobalt-labeled nerve cells and pathways in an invertebrate brain (Sepia officinalis, Cephalopoda). Magn Reson Med 2001;45:575–579.
    External Resources
  26. Willis WD, Al Chaer ED, Quast MJ, Westlund KN: A visceral pain pathway in the dorsal column of the spinal cord. Proc Natl Acad Sci USA 1999;96:7675–7679.
    External Resources
  27. Byrnes K, Li BD, Holm N, Li J, Okadata Y, De Benedetti A, Nedeljkovic-Kurepa A, Mathis M, Chu QD: A novel suicide gene therapy targeting the overexpression of eukaryotic initiation factor 4E improves survival in a rat peritoneal carcinomatosis model. Surgery 2007;142:270–275.
    External Resources
  28. Boyd W: A Textbook of Pathology, Structure and Function in Disease, ed 8. Philadelphia, Lea & Febiger, 1979.
  29. Yamada I, Tsunoda A, Noguchi Y, Komatsuzaki A, Shibuya H: Tumor volume measurements of acoustic neuromas with three-dimensional constructive interference in steady state and conventional spin-echo MR imaging. J Magn Reson Imaging 2000;12:826–832.
    External Resources
  30. Colgan TJ, Pendergast S, Leblanc M: The histopathology of uterine leiomyomas following treatment with gonadotropin-releasing hormone analogs. Hum Pathol 1993;24:1073–1077.
    External Resources
  31. Hassan MH, Salama SA, Arafa HM, Hamada FM, Al-Hendy A: Adenovirus-mediated delivery of a dominant negative estrogen receptor gene in uterine leiomyoma cells abrogates estrogen- and progesterone-regulated gene expression. J Clin Endocrinol Metab 2007;92:3949–3957.
    External Resources
  32. Salama SA, Jamaluddin M, Kumar R, Hassan MH, Al-Hendy A: Progesterone regulates catechol-O-methyl transferase gene expression in breast cancer cells: distinct effect of progesterone receptor isoforms. J Steroid Biochem Mol Biol 2007;107:253–261.
    External Resources
  33. Thornberry NA: The caspase family of cysteine proteases. Br Med Bull 1997;53:478–490.
    External Resources
  34. Sbrana E, Mateo RI, Xiao SY, Popov VL, Newman PC, Tesh RB: Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever. Am J Trop Med Hyg 2006;74:1096–1102.
    External Resources
  35. Alvarez RD, Barnes MN, Gomez-Navarro J, Wang M, Strong TV, Arafat W, Arani RB, Johnson MR, Roberts BL, Siegal GP, Curiel DT: A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial. Clin Cancer Res 2000;6:3081–3087.
    External Resources
  36. Schulick AH, Vassalli G, Dunn PF, Dong G, Rade JJ, Zamarron C, Dichek DA: Established immunity precludes adenovirus-mediated gene transfer in rat carotid arteries: potential for immunosuppression and vector engineering to overcome barriers of immunity. J Clin Invest 1997;99:209–219.
    External Resources
  37. Smith TAG, Mehaffey MG, Kayda DB, Saunders JM, Yei S, Trapnell BC, McClelland A, Kaleko M: Adenovirus-mediated expression of therapeutic plasma levels of human factor-IX in mice. Nat Genet 1993;5:397–402.
    External Resources
  38. Harvey BG, Hackett NR, El-Sawy T, Rosengart TK, Hirschowitz EA, Lieberman MD, Lesser ML, Crystal RG: Variability of human systemic humoral immune responses to adenovirus gene transfer vectors administered to different organs. J Virol 1999;73:6729–6742.
    External Resources
  39. Connolly KM, Bogdanffy MS: Evaluation of proliferating cell nuclear antigen (PCNA) as an endogenous marker of cell proliferation in rat liver: a dual stain comparison with 5-bromo-2′-deoxyuridine. J Histochem Cytochem 1993;41:1–6.
    External Resources
  40. Baldin V, Lukas J, Marcote MJ, Pagano M, Draetta G: Cyclin D1 is a nuclear protein required for cell cycle progression in G1. Genes Dev 1993;7:812–821.
    External Resources
  41. Chang MW, Ohno T, Gordon D, Lu MM, Nabel GJ, Nabel EG, Leiden JM: Adenovirus-mediated transfer of the herpes-simplex virus thymidine kinase gene inhibits vascular smooth muscle cell proliferation and neointima formation following balloon angioplasty of the rat carotid artery. Mol Med 1995;1:172–181.
    External Resources
  42. Aghi M, Hochberg F, Breakefield XO: Prodrug activation enzymes in cancer gene therapy. J Gene Med 2000;2:148–164.
    External Resources
  43. Spencer DM: Developments in suicide genes for preclinical and clinical applications. Curr Opin Mol Ther 2000;2:433–440.
    External Resources
  44. Windeatt S, Southgate TD, Dewey RA, Bolognani F, Perone MJ, Larregina AT, Maleniak TC, Morris ID, Goya RG, Klatzmann D, Lowenstein PR, Castro MG: Adenovirus-mediated herpes simplex virus type-1 thymidine kinase gene therapy suppresses oestrogen-induced pituitary prolactinomas. J Clin Endocrinol Metab 2000;85:1296–1305.
    External Resources
  45. Freytag SO, Barton KN, Brown SL, Narra V, Zhang Y, Tyson D, Nall C, Lu M, Ajlouni M, Movsas B, Kim JH: Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancer. Mol Ther 2007;15:1600–1606.
    External Resources
  46. Yang Y, Ertl HC, Wilson JM: MHC class I-restricted cytotoxic T lymphocytes to viral antigens destroy hepatocytes in mice infected with E1-deleted recombinant adenoviruses. Immunity 1994;1:433–442.
    External Resources
  47. Yang Y, Jooss KU, Su Q, Ertl HC, Wilson JM: Immune responses to viral antigens versus transgene product in the elimination of recombinant adenovirus-infected hepatocytes in vivo. Gene Ther 1996;3:137–144.
    External Resources
  48. Worgall S, Leopold PL, Wolff G, Ferris B, Van Roijen N, Crystal RG: Role of alveolar macrophages in rapid elimination of adenovirus vectors administered to the epithelial surface of the respiratory tract. Hum Gene Ther 1997;8:1675–1684.
    External Resources
  49. Chen HH, Mack LM, Kelly R, Ontell M, Kochanek S, Clemens PR: Persistence in muscle of an adenoviral vector that lacks all viral genes. Proc Natl Acad Sci USA 1997;94:1645–1650.
    External Resources
  50. Hassan MH, Khatoon N, Curiel DT, Hamada FM, Arafa HM, Al-Hendy A: Toward gene therapy of uterine fibroids: targeting modified adenovirus to human leiomyoma cells. Hum Reprod 2008;23:514–524.
    External Resources
  51. Reed JC, Jurgensmeier JM, Matsuyama S: Bcl-2 family proteins and mitochondria. Biochim Biophys Acta 1998;1366:127–137.
    External Resources
  52. Knudson CM, Korsmeyer SJ: Bcl-2 and Bax function independently to regulate cell death. Nat Genet 1997;16:358–363.
    External Resources
  53. Monney L, Otter I, Olivier R, Ravn U, Mirzasaleh H, Fellay I, Poirier GG, Borner C: Bcl-2 overexpression blocks activation of the death protease CPP32/Yama/apopain. Biochem Biophys Res Commun 1996;221:340–345.
    External Resources
  54. Nomura M, Shimizu S, Ito T, Narita M, Matsuda H, Tsujimoto Y: Apoptotic cytosol facilitates Bax translocation to mitochondria that involves cytosolic factor regulated by Bcl-2. Cancer Res 1999;59:5542–5548.
    External Resources
  55. Wu X, Blanck A, Olovsson M, Henriksen R, Lindblom B: Expression of Bcl-2, Bcl-x, Mcl-1, Bax and Bak in human uterine leiomyomas and myometrium during the menstrual cycle and after menopause. J Steroid Biochem Mol Biol 2002;80:77–83.
    External Resources
  56. Khurana KK, Singh SB, Tatum AH, Schulz V, Badawy SZ: Maintenance of increased Bcl-2 expression in uterine leiomyomas after GnRH agonist therapy. J Reprod Med 1999;44:487–492.
    External Resources
  57. Bouchard WJ, Rouleau M, Poirier GG: PARP-1, a determinant of cell survival in response to DNA damage. Exp Hematol 2003;31:446–454.
    External Resources
  58. Chiarugi A: Poly(ADP-ribose) polymerase: killer or conspirator? The suicide hypothesis revisited. Trends Pharmacol Sci 2002;23:122–129.
    External Resources
  59. Soldani C, Scovassi AI: Poly(ADP-ribose) polymerase-1 cleavage during apoptosis: an update. Apoptosis 2002;7:321–328.
    External Resources
  60. Huang SC, Tang MJ, Cheng YM, Hsu KF, Ho CL, Chou CY: Enhanced polyadenosine diphosphate-ribosylation in gonadotropin-releasing hormone agonist-treated uterine leiomyoma. J Clin Endocrinol Metab 2003;88:5009–5016.
    External Resources
  61. Shanmugathasan M, Jothy S: Apoptosis, anoikis and their relevance to the pathobiology of colon cancer. Pathol Int 2000;50:273–279.
    External Resources
  62. Dixon D, Flake GP, Moore AB, He H, Haseman JK, Risinger JI, Lancaster JM, Berchuck A, Barrett JC, Robboy SJ: Cell proliferation and apoptosis in human uterine leiomyomas and myometria. Virchows Arch 2002;441:53–62.
    External Resources
  63. Loy CJ, Evelyn S, Lim FK, Liu MH, Yong EL: Growth dynamics of human leiomyoma cells and inhibitory effects of the peroxisome proliferator-activated receptor-gamma ligand, pioglitazone. Mol Hum Reprod 2005;11:561–566.
    External Resources
  64. Kurki P, Vanderlaan M, Dolbeare F, Gray J, Tan EM: Expression of proliferating cell nuclear antigen (PCNA)/cyclin during the cell cycle. Exp Cell Res 1986;166:209–219.
    External Resources
  65. Raper SE, Yudkoff M, Chirmule N, Gao GP, Nunes F, Haskal ZJ, Furth EE, Propert KJ, Robinson MB, Magosin S, Simoes H, Speicher L, Hughes J, Tazelaar J, Wivel NA, Wilson JM, Batshaw ML: A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther 2002;13:163–175.
    External Resources
  66. Worgall S, Wolff G, Falck-Pedersen E, Crystal RG: Innate immune mechanisms dominate elimination of adenoviral vectors following in vivo administration. Hum Gene Ther 1997;8:37–44.
    External Resources
  67. Abbas AK, Murphy KM, Sher A: Functional diversity of helper T lymphocytes. Nature 1996;383:787–793.
    External Resources
  68. Harty JT, Tvinnereim AR, White DW: CD8(+) T cell effector mechanisms in resistance to infection. Annu Rev Immunol 2000;18:275–308.
    External Resources
  69. Radoja S, Frey AB, Vukmanovic S: T-Cell receptor signaling events triggering granule exocytosis. Crit Rev Immunol 2006;26:265–290.
    External Resources
  70. Yang Y, Li Q, Ertl HC, Wilson JM: Cellular and humoral immune responses to viral antigens create barriers to lung-directed gene therapy with recombinant adenoviruses. J Virol 1995;69:2004–2015.
    External Resources
  71. Harvey BG, et al: Host responses and persistence of vector genome following intrabronchial administration of an E1(–)E3(–) adenovirus gene transfer vector to normal individuals. Mol Ther 2001;3:206–215.
    External Resources
  72. Roth DA, et al: Intracoronary delivery of an adenovirus encoding fibroblast growth factor-4 in myocardial ischemia: Effect of serum antibodies and previous exposure to adenovirus. Hum Gene Ther 2006;17:230– 238.
    External Resources
  73. Huard J, Lochmuller H, Acsadi G, Jani A, Massie B, Karpati G: The route of administration is a major determinant of the transduction efficiency of rat tissues by adenoviral recombinants. Gene Ther 1995;2:107– 115.
    External Resources
  74. Sullivan DM, Jensen TG, Taichman LB, Csaky KG: ornithine-delta-aminotransferase expression and ornithine metabolism in cultured epidermal keratinocytes: toward metabolic sink therapy for gyrate atrophy. Gene Ther 1997;4:1036–1044.
    External Resources
  75. Sterman DH, Recio A, Vachani A, Sun J, Cheung L, DeLong P, Amin KM, Litzky LA, Wilson JM, Kaiser LR, Albelda SM: Long-term follow-up of patients with malignant pleural mesothelioma receiving high-dose adenovirus herpes simplex thymidine kinase/ganciclovir suicide gene therapy. Clin Cancer Res 2005;11:7444–7453.
    External Resources
  76. Ayala G, Satoh T, Li R, Shalev M, Gdor Y, Aguilar-Cordova E, Frolov A, Wheeler TM, Miles BJ, Rauen K, Teh BS, Butler EB, Thompson TC, Kadmon D: Biological response determinants in HSV-tk + ganciclovir gene therapy for prostate cancer. Mol Ther 2006;13:716–728.
    External Resources
  77. Nasu Y, Saika T, Ebara S, Kusaka N, Kaku H, Abarzua F, Manabe D, Thompson TC, Kumon H: Suicide gene therapy with adenoviral delivery of HSV-tK gene for patients with local recurrence of prostate cancer after hormonal therapy. Mol Ther 2007;15:834–840.
    External Resources
  78. Hiltunen MO, Turunen MP, Turunen AM, Rissanen TT, Laitinen M, Kosma VM, Yla-Herttuala S: Biodistribution of adenoviral vector to nontarget tissues after local in vivo gene transfer to arterial wall using intravascular and periadventitial gene delivery methods. FASEB J 2000;14:2230–2236.
    External Resources
  79. Othman EE, Zhu ZB, Curiel DT, Khatoon N, Salem HT, Khaifa EA, Al-Hendy A: Toward gene therapy of endometriosis; transductional and transcriptional targeting of adenoviral vectors to endometriosis cells. Am J Obstet Gynecol 2008;117:e1–e6.
  80. Goodwin SC, Walker WJ: Uterine artery embolization for the treatment of uterine fibroids. Curr Opin Obstet Gynecol 1998;10:315–320.
    External Resources
  81. Hutchins FL Jr, Worthington-Kirsch R, Berkowitz RP: Selective uterine artery embolization as primary treatment for symptomatic leiomyomata uteri. J Am Assoc Gynecol Laparosc 1999;6:279–284.
    External Resources
  82. Verma IM, Weitzman MD: Gene therapy: twenty-first century medicine. Annu Rev Biochem 2005;74:711–738.
    External Resources
  83. Journal of Gene Medicine: website at http://www.wiley.co.uk/wileychi/genmed.
  84. Micheff M, Tchakaraov S, Zoubak S, Loukinov D, Botev C, Altankov I, Georgiev G, Petrov S, Meryman HT: Naked DNA and adenoviral immunizations for immunotherapy of prostate cancer: a phase I/II clinical trial. Eur Urol 2000;38:208–217.
    External Resources
  85. Stephenson JR: Genetically modified viruses: vaccines by design. Curr Pharm Biotechnol 2001;2:47–76.
    External Resources
  86. Stribley JM, Rehman KS, Niu H, Christman GM: Gene therapy and reproductive medicine. Fertil Steril 2002;77:645–657.
    External Resources
  87. Wivel NA, Wilson JM. Methods of gene delivery. Hematol Oncol Clin North Am 1998;12:483–501.
    External Resources
  88. Nielsen LL, Lipari P, Dell J, Gurnani M, Hajian G: Adenovirus-mediated p53 gene therapy and paclitaxel have synergistic efficacy in models of human head and neck, ovarian, prostate, and breast cancer. Clin Cancer Res 1998;4:835–846.
    External Resources
  89. Kunishige I, Samejima Y, Shiki Y, Moriyama A, Meruelo D, Saji F, Murata Y: Suicide gene therapy for human uterine adenocarcinoma cells using herpes simplex virus thymidine kinase. Gynecol Oncol 1999;72:16–25.
    External Resources
  90. Ramondetta L, Mills GB, Burke TW, Wolf JK: Adenovirus-mediated expression of p53 or p21 in a papillary serous endometrial carcinoma cell line (SPEC-2) results in both growth inhibition and apoptotic cell death: potential application of gene therapy to endometrial cancer. Clin Cancer Res 2000;6:278–284.
    External Resources
  91. Lazennec G, Alcorn JL, Katzenellenbogen BS: Adenovirus-mediated delivery of a dominant negative estrogen receptor gene abrogates estrogen-stimulated gene expression and breast cancer cell proliferation. Mol Endocrinol 1999;13:969–980.
    External Resources
  92. Au WW, Abdou-Salama S, Al-Hendy A: Inhibition of growth of cervical cancer cells using a dominant negative estrogen receptor gene. Gynecol Oncol 2007;104:276–280.
    External Resources
  93. Othman ER, Salama S, Ismail N, Al-Hendy A: Gene Therapy of endometriosis: adenovirus mediated expression of dominant negative estrogen receptor induces apoptosis in human endometriotic cells. Fertil Steril 2007;88:462–471.
    External Resources
  94. Ghadami M, Salama SA, Khatoon N, Chilvers R, Nagamani M, Chedrese PJ, Al-Hendy A: Toward gene therapy of primary ovarian failure: adenovirus expressing human FSH receptor corrects the Finnish C566T mutation. Mol Hum Reprod 2008;14:9–15.
    External Resources
  95. Saed GM, Al-Hendy A, Salama SA, Diamond MP: Adenovirus-mediated expression of cyclooxygenase-2 antisense reverse abnormal genetic profile of human adhesion fibroblasts. Fertil Steril 2008;89(suppl):1455–1460.
    External Resources
  96. Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, et al: Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science 2000;288:669–672.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Original Article

Received: December 28, 2007
Accepted: November 27, 2008
Published online: March 27, 2009
Issue release date: July 2009

Number of Print Pages: 14
Number of Figures: 7
Number of Tables: 1

ISSN: 0378-7346 (Print)
eISSN: 1423-002X (Online)

For additional information: https://www.karger.com/GOI

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

2009, Vol.68, No. 1

July 2009

Article

Recommend This
TOP