BACKGROUND: Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. STUDY DESIGN: This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN). RESULTS: Ad-ER-DN transduction, in both human and rat leiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, rat leiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ-treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN-treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index). CONCLUSION: Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
BACKGROUND:Leiomyomas (fibroids) are common estrogen-dependent uterine tumors with no effective medicinal treatment; hysterectomy is the mainstay of management. STUDY DESIGN: This study was undertaken to investigate a potential therapy for leiomyoma; we used a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN). RESULTS: Ad-ER-DN transduction, in both human and ratleiomyoma cell lines, induced an increase in both caspase-3 levels and BAX/Bcl-2 ratio with evident apoptosis in the TdT-mediated dUTP nick-end labeling assay. In nude mice, ratleiomyoma cells ex vivo transduced with Ad-ER-DN supported significantly smaller tumors compared with Ad-LacZ-treated cells 5 weeks after implantation. In mice treated by direct intratumor injection into preexisting lesions, Ad-ER-DN caused immediate overall arrest of tumor growth. The Ad-ER-DN-treated tumors demonstrated severely inhibited cell proliferation (BrdU index) and a marked increase in the number of apoptotic cells (TdT-mediated dUTP nick-end labeling index). CONCLUSION: Dominant-negative estrogen receptor gene therapy may provide a nonsurgical treatment option for women with symptomatic uterine fibroids who want to preserve their uteri.
Authors: Essam-Eldin R Othman; Zeng B Zhu; David T Curiel; Nilufar Khatoon; Hosam T Salem; Essam Al-Din M Khalifa; Ayman Al-Hendy Journal: Am J Obstet Gynecol Date: 2008-08 Impact factor: 8.661
Authors: Erica N Nierth-Simpson; Melvenia M Martin; Tung-Chin Chiang; Lilia I Melnik; Lyndsay V Rhodes; Shannon E Muir; Matthew E Burow; John A McLachlan Journal: Endocrinology Date: 2009-01-29 Impact factor: 4.736
Authors: Nicole M Fletcher; Mohammed G Saed; Suleiman Abuanzeh; Husam M Abu-Soud; Ayman Al-Hendy; Michael P Diamond; Ghassan M Saed Journal: Reprod Sci Date: 2014-02-11 Impact factor: 3.060
Authors: Memy H Hassan; Salama A Salama; Dong Zhang; Hossam M M Arafa; Farid M A Hamada; Hala Fouad; Cheryl C Walker; Ayman Al-Hendy Journal: Fertil Steril Date: 2009-01-14 Impact factor: 7.329
Authors: M Ghadami; E El-Demerdash; S A Salama; A A Binhazim; A E Archibong; X Chen; B R Ballard; M R Sairam; A Al-Hendy Journal: Mol Hum Reprod Date: 2010-01-19 Impact factor: 4.025