Research

RECENT PUBLICATIONS ON THE TOPIC OF TREATMENTS FOR UTERINE LEIOMYOMA

Taylor D, Leppert PC.  Treatment for Uterine Fibroids: Searching for Effective Drug Therapies. Drug Discovery Today: Therapeutic Strategies. 2012. 10.1016/jddstr. 2012.06.001; 2012: 9 (1) e41-e49.

  • This paper includes information regarding all therapies including herbal and traditional Chinese Medicine treatments, with a discussion of the active ingredient in green tea. The pharmacological and biochemical mechanisms of action are also address.

Singh SS, Belland L. Contemporary management of uterine fibroids: focus on emerging medical treatments. Curr Med Res Opin 2014 Nov 12 1-12 EPub ahead of print.

  • The authors reviewed articles published from 1980 to 2012 with a focus on emerging medical therapies. They emphasize their conviction that medical therapies could replace surgical intervention.

Moroni R, Vieria C, Ferriani R, Candido-Dos-Reis F, Brito L. Pharmacological treatment of uterine fibroids. Ann Med Health Sci Res 2014, S-185 92.

  • A comprehensive review of multiple databases allowed the authors to discuss 41 clinical trials of therapies.

Patel A, Malik M, Britten J, Cox J, Catherino WH. Alternate therapies in management of leiomyomas. Fertil Steril. 2014, 102:649-655.

  • The authors present mri-guided focused ultrasound surgery, cryomolysis, inclusion of uterine arteries and discuss procedure techniques, patient eligibility, complications and outcomes.

Guo SC, Segars JH. The impact and management of fibroids for fertility: an evidence based approach. Obstet Gynecol Clin North Am. 2012, 39:521-533.

  • This is a paper with good discussions of fertility issues related to leiomyoma management.  The authors stress the need for additional treatment options.  State that currently myomectomy is the option that is most effective for women desiring pregnancy.

Chaubert-Buffet N, Esber N, Bouchard P. Fibroid growth and medical options for treatment. Fertil Steril 2014, 102: 630-639.

  • Especially good discussions of intrauterine progestin delivery to reduce bleeding, GnRH analogues and selective progesterone receptor modulators are found in this paper.

Stine JE, Clarke-Pearson DL, Gehrig PA. Uterine morcellation at the time of hysterectomy: techniques, risks, and recommendations. Obstet Gynecol Sur 2014, 69:415-425.

  • This paper presents an careful approach to uterine leiomyoma morcellation from the point of view of gynecologic oncologists with specific recommendations.  It is important reading for all clinicians who treat women with uterine leiomyoma.

 

 

CURRENT RESEARCH
One of the primary goals of the Leppert Foundation is the provide and sponsor research that will lead to healthier lives, pregnancies, and births.  Research conducted by members of our board of directors is published in peer-reviewed journals and presented at conferences nationwide.

“Feeling the force” in reproduction: Mechanotransduction in reproductive processes.
Janice P. Evans, Phyllis C. Leppert
Reproductive biologists are well-versed in many types of biochemical signaling, and indeed, there are almost innumerable examples in reproduction, including steroid and peptide hormone signaling, receptor-ligand and secondary messenger-mediated signaling, signaling regulated by membrane channels, and many others. Among reproductive scientists, a perhaps lesser-known but comparably important mode of signaling is mechanotransduction: the concept that cells can sense and respond to externally applied or internally generated mechanical forces. Given the cell shape changes and tissue morphogenesis events that are components of many phenomena in reproductive function, it should be no surprise that mechanotransduction has major impacts in reproductive health and pathophysiology. The conference on “Mechanotransduction in the Reproductive Tract” was a valuable launch pad to bring this hot issue in development, cell biology, biophysics, and tissue regeneration to the realm of reproductive biology. The goal of the meeting was to stimulate interest and increased mechanotransduction research in the reproductive field by presenting a broad spectrum of responses impacted by this process. The meeting highlighted the importance of convening expert investigators, students, fellows, and young investigators from a number of research areas resulting in cross-fertilization of ideas and suggested new avenues for study. The conference included talks on tissue engineering, stem cells, and several areas of reproductive biology, from uterus and cervix to the gametes. Specific reproductive health-relevant areas, including uterine fibroids, gestation and parturition, and breast tissue morphogenesis, received particular attention.

Treatment for uterine fibroids: Searching for effective drug therapies
Darlene K. Taylor, Phyllis C. Leppert
Drug Discovery Today: Therapeutic Strategies, 2012
Uterine fibroids are common reproductive-age benign tumors that contribute to severe morbidity and infertility. Cumulative incidence is 4 times higher in African- Americans compared to Caucasians and constitutes a major health disparity challenge. Fibroids are the lead- ing indication for hysterectomy and their management averages $21 billion annually in the US. No long term minimally invasive therapies exist. Thus, promising drug therapies, their chemistry, pharmacology, and clinical efficacy, focusing first on innovative drug delivery approaches, are reviewed.

Myometrial Hyperplasia Mimics the Clinical Presentation of Uterine Fibroids: A Report of 3 Cases
Patricia M. Newcomb, M.D., Stewart F. Cramer, M.D., and Phyllis C. Leppert, M.D., Ph.D.
International Journal of Gynecological Pathology, 2013
The clinical diagnosis of fibroid uterus is based on physical examination findings and/or ultrasound. However, it is not uncommon for routine pathology examination to report no significant fibroids in such cases. Myometrial hyperplasia (MMH) is a structural variation with irregular zones of hypercellularity and increased nucleus/cell ratio that appears in adolescence, can progress during the childbearing years, and can sometimes cause grossly detectable bulges on pathologic examination.

Mechanical homeostasis is altered in uterine leiomyoma
Rebecca Rogers, BS; John Norian, MD; Minnie Malik, PhD; Gregory Christman, MD; Mones Abu-Asab, PhD; Faye Chen, PhD; Casey Korecki, MSME; James Iatridis, PhD; William H. Catherino, MD, PhD; Rocky S. Tuan, PhD; Namisha Dhillon; Phyllis Leppert, MD, PhD; James H. Segars, MD
American Journal of Obstetrics & Gynecology, 2008
Uterine leiomyoma produce an extracellular matrix (ECM) that is abnormal in its volume, content, and structure. Alterations in ECM can modify mechanical stress on cells and lead to activation of Rho-dependent signaling and cell growth. Here we sought to determine whether the altered ECM that is produced by leiomyoma was accompanied by an altered state of mechanical homeostasis.

The estimated annual cost of uterine leiomyomata in the United States
Eden R. Cardozo, MD; Andrew D. Clark, MD, PhD; Nicole K. Banks, MD; Melinda B. Henne, MD, MS; Barbara J. Stegmann, MD, MPH; James H. Segars, MD
American Journal of Obstetrics & Gynecology, 2012
The purpose of this study was to estimate the total annual societal cost of uterine fibroid tumors in the United States, based on direct and indirect costs that include associated obstetric complications.

Characterization of tissue biomechanics and mechanical signaling in 2 uterine leiomyoma
John M. Norian, Carter M. Owen, Juan Taboas, Casey Korecki, Rocky Tuan, Minnie Malik, William H. Catherino, James H. Segars
Matrix Biology (2011)
Leiomyoma are common tumors arising within the uterus that feature excessive deposition of a stiff, disordered 31 extracellularmatrix (ECM).Mechanical stress is a critical determinant of excessive ECMdeposition and increased 32 mechanical stress has been shown to be involved in tumorigenesis. Here we tested the viscoelastic properties of 33 leiomyoma and characterized dynamic and static mechanical signaling in leiomyoma cells using three ap- 34 proaches, including measurement of active RhoA.