Uterine Fibroids (Leiomyomata) and Heavy Menstrual Bleeding (original) (raw)
Related papers
Angiogenesis and pro-angiogenic factors in uterine fibroids - facts and myths
Folia medica Cracoviensia
Uterine leiomyomata present major problem for females. Although they are benign tumors their frequency is associated with many symptoms like infertility, abdominal pain, menorrhagia. Authors based on their own morphological studies and review of the literature try to indicate main factors causing angiogenesis within leiomyomata and its influence on tumor growth. The strongest proangiogenic factor seems to be hypoxia, which stimulates up- and down-regulation of numerous genetically determined substances. Also mechanical pressure acting upon newly growing vessels is one of the factors which may determine formation of so called "vascular pseudocapsule" around the lesion.
Journal of the Turkish German Gynecology Association, 2013
Uterine fibroids (UF) are the most common gynecological tumors in premenopausal women. Hysterectomy remains the major and definitive therapeutic option. Minimally invasive surgical techniques for performing hysterectomy have many advantages over laparotomy. Current drug therapies for UF remain unsatisfactory. Unquestionably, continued investigation of novel agents is necessary. The currently used drugs for UF treatment which exclusively modulate a single target, typically either the estrogen or progesterone signaling pathways, are limited in their therapeutic effects. By contrast, multi-target drugs which simultaneously modulate multiple critical hubs in the network of the signaling pathways underlying UF pathogenesis should achieve robust and durable therapeutic effects.
Comprehensive Review of Uterine Fibroids: Developmental Origin, Pathogenesis, and Treatment
Endocrine Reviews, 2021
Uterine fibroids are benign monoclonal neoplasms of the myometrium, representing the most common tumors in women worldwide. To date, no long-term or noninvasive treatment option exists for hormone-dependent uterine fibroids, due to the limited knowledge about the molecular mechanisms underlying the initiation and development of uterine fibroids. This paper comprehensively summarizes the recent research advances on uterine fibroids, focusing on risk factors, development origin, pathogenetic mechanisms, and treatment options. Additionally, we describe the current treatment interventions for uterine fibroids. Finally, future perspectives on uterine fibroids studies are summarized. Deeper mechanistic insights into tumor etiology and the complexity of uterine fibroids can contribute to the progress of newer targeted therapies.
Molecular Human Reproduction
Basic fibroblast growth factor (bFGF) is a regulator of angiogenesis which is overexpressed in leiomyomas compared with matched myometrium. To understand the physiological significance of this finding we characterized the expression of the type 1 receptor for this ligand (FGFR1). Utilizing reverse transcription-polymerase chain reaction (RT-PCR) we identified the complete and alternatively spliced transmembrane forms and two secreted forms of the FGFR1 in endometrium, myometrium and leiomyomas from all patients. This is the first report of secreted forms in uterine tissue. Proteins consistent with each of these isoforms were identified by Western blot analysis in all three tissues. Immunohistochemistry revealed menstrual cycle-specific regulation of FGFR1 protein in the endometrial stroma of normal women but not in women with leiomyomas and abnormal uterine bleeding. Stromal FGFR1 expression is suppressed in the early luteal phase in normal women, but not in women with leiomyoma-rel...
Subtype-Specific Tumor-Associated Fibroblasts Contribute to the Pathogenesis of Uterine Leiomyoma
Cancer research, 2017
Recent genomic studies have identified subtypes of uterine leiomyoma (LM) with distinctive genetic alterations. Here, we report the elucidation of the biological characteristics of the two most prevalent uterine leiomyoma subtypes, MED12-mutant (MED12-LM) and HMGA2-overexpressing (HMGA2-LM) uterine leiomyomas. Because each tumor carries only one genetic alteration, both subtypes are considered to be monoclonal. Approximately 90% of cells in HMGA2-uterine leiomyoma were smooth muscle cells (SMC) with HMGA2 overexpression. In contrast, MED12-LM consisted of similar numbers of SMC and non-SMC, which were mostly tumor-associated fibroblasts (TAF). Paradoxically, TAF carried no mutations in MED12, suggesting an interaction between SMC and TAF to coordinate their growth. The higher amount of extracellular matrix in MED12-LM than HMGA2-LM was partially due to the high concentration of collagen-producing TAF. SMC growth in a xenograft assay was driven by progesterone in both uterine leiomyo...
Fibroids: pathophysiology and current medical treatment
Baillière's best practice & research. Clinical obstetrics & gynaecology, 1999
Uterine leiomyomas, or fibroids, are a major cause of abnormal uterine bleeding in women. These benign tumours develop during the reproductive years and their growth has been shown to be dependent on the ovarian steroid hormones oestradiol and progesterone. The growth promoting effects of these steroid hormones appear to be mediated through the local production of specific growth factors. Traditional treatment for leiomyomas has been surgical removal through either hysterectomy or myomectomy. Newer surgical techniques, such as hysteroscopic removal of leiomyomas, endometrial ablation, or uterine arterial embolization, are now being tested as effective but less invasive methods of treatment. Non-surgical treatment of leiomyomas has been primarily through the use of gonadotrophin-releasing hormone agonists which suppress circulating oestradiol and progesterone levels by shutting down the pituitary-ovarian axis. The suppression in steroid hormone levels results in significant fibroid s...
Vascular density, angiogenesis and pro-angiogenic factors in uterine fibroids
Folia medica Cracoviensia, 2016
Angiogenesis is a process of development of new vessels from the preexisting vascular network of a host. This is process which is seen in many physiological situations but it accompanies also a development of different lesions, i.e. neoplasms. Uterine fibroids are one of the most frequent lesions which affect human internal female genital tracts. Authors briefly review most important pro-angiogenic factors, based on their own observation as well as reviewing current literature. They pay much attention to vascular density which is significantly changed in the uterine tumors.
The genetic bases of uterine fibroids; a review
Journal of reproduction & infertility, 2011
Uterine leiomyomas/fibroids are the most common pelvic tumors of the female genital tract. The initiators remaining unknown, estrogens and progesterone are considered as promoters of fibroid growth. Fibroids are monoclonal tumors showing 40-50% karyo-typically detectable chromosomal abnormalities. Cytogenetic aberrations involving chromosomes 6, 7, 12 and 14 constitute the major chromosome abnormalities seen in leiomyomata. This has led to the discovery that disruptions or dysregulations of HMGIC and HMGIY genes contribute to the development of these tumors. Genes such as RAD51L1 act as translocation partners to HMGIC and lead to disruption of gene structure leading to the pathogenesis of uterine fibroids. The mechanism underlying this disease is yet to be identified. The occurrence of PCOLCE amid a cluster of at least eight Alu sequences is potentially relevant to the possible involvement of PCOLCE in the 7q22 rearrangements that occur in many leiomyomata. PCOLCE is implicated in c...
Exploring uterine fibroids and its treatment in current scenario
IP International Journal of Comprehensive and Advanced Pharmacology
Uterine Fibroids (leiomyoma) are made of muscle cells and other grow tissues grow in and around of the wall of the uterus. Uterine fibroids benign tumors in women reproduction age worldwide. Many are discovered incidentally on clinically examination. Approximately 30% of women with uterine fibroids will present with severe symptoms, which can include abdominal uterine bleeding, anemia, pelvic pain and constipation. Infertility and recurrent miscarriage may also be symptoms of fibroids, depending on their location and size, especially for sub mucous and intramural myelomas distorting the uterine cavity. Current option for symptomatic fibroid treatment includes expectant medical and surgical management radiology procedures. Ultrasound can be done, when a patient is symptomatic of uterine fibroids. Fibroids are generally classified by their location; intramural fibroids, subserosal fibroids, submucosal fibroids. The cause of uterine fibroids is unknown, But research and clinical experi...
Human Reproduction Update, 2014
† Introduction † Overview of uterine fibroids Molecular etiology and potential therapeutic targets for uterine fibroids Treatment of uterine fibroids † Epidemiology, genetics and environment Finding genes for uterine fibroids Uterine fibroids and the exposure paradigm Epidemiologic insights into ethnic differences in uterine fibroid burden Risk factors for uterine fibroids in the Black Women's Health Study Race and fibroid tumor burden † Pathogenesis: growth factors, cytokines, cell signaling and the extracellular matrix Mediators and integrators of the molecular microenvironment in uterine fibroids Growth factor signaling pathways in uterine fibroids Regulation of growth factor signaling pathways in uterine fibroids by endogenous and environmental factors † Hormonal regulation and hormone receptor interactions † Developing new model systems Green tea extract for the treatment of uterine fibroids Uterine b-catenin mouse model for uterine fibroids Mouse xenograft model for human uterine fibroids