NEW YORK (Reuters Health) - In an animal model of uterine leiomyoma, localized treatment with gene therapy that inactivates the tumor’s estrogen receptors causes the tumors to shrink, according to a report in the November issue of the American Journal of Obstetrics and Gynecology.
Uterine fibroids are seen “more and more in women who either haven’t completed their family or have not even had their first pregnancy,” lead author Dr. Ayman Al-Hendy told Reuters Health. The problem is that “most current treatments -- hysterectomy or uterine artery embolization -- end the fertility potential of those women.”
Dr. Al-Hendy, of the University of Texas Medical Branch in Galveston, and colleagues treated rat leiomyoma cells with a mutated dominant-negative estrogen receptor gene delivered via an adenoviral vector (Ad-ER-DN) and then injected them subcutaneously into nude mice. The tumors that grew were significantly smaller compared with those in mice treated with control cells (p < 0.0001).
The team also grew tumors in mice for approximately 2 to 3 weeks, and then injected the tumors directly with Ad-ER-DN, a control adenovirus Ad-Lac-Z or carrier. Beginning as early as 1 week after virus treatment, tumors in the Ad-ER-DN animals were significantly smaller than those in the control groups.
“Ad-ER-DN directly injected into preexisting leiomyoma tumors,” say the investigators, “causes immediate and sustained arrest of tumor growth accompanied by dramatic inhibition of cell proliferation and increased apoptosis.”
Furthermore, animals in the control group exhibited cachexia, malaise and skin ulceration at 3 weeks after treatment, whereas those treated with Ad-ER-DN appeared healthy.
Experiments, in which leiomyoma cells were grown in cell culture, showed that treatment with Ad-ER-DN led to arrested cell proliferation and induced cell death. Further evaluation revealed that treatment caused a decrease in the amount of the antiapoptotic Bcl-2 protein and an increase in the proapoptotic Bax protein, and higher levels of caspase-3, an effector of apoptosis.
The authors note that leiomyoma is an attractive target for gene therapy because the disease is localized and easily targeted by intratumor injection. Moreover, clinical improvement does not require complete resolution of the tumor, as even a modest decrease in size decreases symptoms.
The treatment “should not interfere with the fertility potential of the patient,” Dr. Al-Hendy concluded. “Patients who still want to become pregnant represent a group who we have failed so far, and we hope with this approach that we’ll have an option for them for the future.”
Source: Am J Obstet Gynecol 2004;191:1621-1631. [ Google search on this article ]
MeSH Headings:Biological Therapy: Genetic Engineering: Genetic Techniques: Investigative Techniques: Receptors, Estrogen: Receptors, Steroid: Therapeutics: Transcription Factors: Gene Therapy: Receptors, Cytoplasmic and Nuclear: Analytical, Diagnostic and Therapeutic Techniques and EquipmentCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
