Parity associates with chromosomal damage in uterine leiomyomas.
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ABSTRACT:
SUBMITTER: Kuisma H
PROVIDER: S-EPMC8440576 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectiveTo determine the frequency of uterine leiomyomas and hysterectomy in patients with lymphangioleiomyomatosis (LAM), a disease characterized by proliferation of abnormal-appearing smooth muscle-like cells.DesignRetrospective study.SettingNatural history study at the National Institutes of Health.Patient(s)456 patients with sporadic LAM and LAM associated with tuberous sclerosis complex (LAM/TSC).Intervention(s)Review of records and pelvic computed axial tomography scans.Main outcome measure(s)Prevalence of uterine leiomyomas and hysterectomy.Result(s)A total of 174 women had uterine leiomyomas (38%). One hundred eighteen were diagnosed by computed tomographic scan and 56 were diagnosed by hysterectomy. Among 323 patients who did not have hysterectomy, 105 of 270 patients (39%) with sporadic LAM and 13 of 53 (25%) with LAM/TSC had uterine leiomyomas. Hysterectomy was performed in 108 of 378 subjects with sporadic LAM and 25 of 78 with LAM/TSC. Fifty-six patients were found to have uterine fibroids on hysterectomy. The most common indications for hysterectomy were uterine leiomyoma, LAM, and endometriosis.Conclusion(s)Uterine leiomyomas are not more common in LAM than in the general population. However, in LAM, the frequency of hysterectomy is higher because of it having been recommended for treatment of LAM.
| S-EPMC3165169 | biostudies-literature
Project description:BackgroundUterine leiomyomas can be classified into molecularly distinct subtypes according to their genetic triggers: MED12 mutations, HMGA2 upregulation, or inactivation of FH. The aim of this study was to identify metabolites and metabolic pathways that are dysregulated in different subtypes of leiomyomas.MethodsWe performed global metabolomic profiling of 25 uterine leiomyomas and 17 corresponding myometrium specimens using liquid chromatography-tandem mass spectroscopy.ResultsA total of 641 metabolites were detected. All leiomyomas displayed reduced homocarnosine and haeme metabolite levels. We identified a clearly distinct metabolomic profile for leiomyomas of the FH subtype, characterised by metabolic alterations in the tricarboxylic acid cycle and pentose phosphate pathways, and increased levels of multiple lipids and amino acids. Several metabolites were uniquely elevated in leiomyomas of the FH subtype, including N6-succinyladenosine and argininosuccinate, serving as potential biomarkers for FH deficiency. In contrast, leiomyomas of the MED12 subtype displayed reduced levels of vitamin A, multiple membrane lipids and amino acids, and dysregulation of vitamin C metabolism, a finding which was also compatible with gene expression data.ConclusionsThe study reveals the metabolomic heterogeneity of leiomyomas and provides the requisite framework for strategies designed to target metabolic alterations promoting the growth of these prevalent tumours.
| S-EPMC5729474 | biostudies-literature
Project description:Uterine leiomyomas are common and life-altering for many women. Despite a wide range of symptoms, varying characteristics of the uterus and the leiomyomas themselves, and many alternatives, hysterectomy accounts for almost three fourths of all surgical therapy, yet there is increasing evidence for a variety of procedural therapies for symptomatic leiomyomas and a new generation of medical therapies under development. With increasing evidence of long-term risk from hysterectomy and new data regarding leiomyoma biology, individualized medical approaches to leiomyomas are likely in the near future. Key biological attributes that influence this disease process are common driver mutations and the new appreciation of the interaction of smooth muscle cells and fibroblasts. Additionally, the interaction between cell types and steroid hormone responsiveness likely plays a role in pathogenesis that can be leveraged in individualized therapy. However, given the independent clonal nature of leiomyomas within the same uterus, moving in the direction of biopsies for individual leiomyomas to understand the biology is unlikely to be fruitful. Use of advanced imaging will likely continue to evolve not only to accurately predict malignant disease, including sarcomas, but to predict leiomyoma subtypes, response to therapy, or both. We predict the continued evolution of therapy from excisional or interventional therapies to medical therapies and ultimately prediction of at-risk individuals. Ideally, individualized therapies will offer primary prevention for women at high risk of leiomyomas and secondary prevention after initial treatment.
| S-EPMC6153058 | biostudies-literature
Project description:BackgroundUterine leiomyomas and adenomyosis are both common and often associated with abnormal uterine bleeding (AUB), including the symptom of heavy menstrual bleeding (HMB). Understanding the prevalence of adenomyosis in women with uterine leiomyomas could inform clinicians and patients in a way that may improve therapeutic approaches.ObjectiveTo explore the prevalence of adenomyosis in a group of women who underwent hysterectomy for AUB-L, to determine the prevalence of submucous leiomyomas, and to examine the utility of preoperative ultrasound to detect the presence of adenomyosis.MethodsThe Kaiser Permanente Hysterectomy Database (KPHD) was searched for women aged 18-52 undergoing hysterectomy for leiomyoma-associated chronic AUB (AUB-L) in 2018 and 2019. A target sample of 400 comprised those with at least 3 years in the Health System. Radiologists evaluated preoperative pelvic ultrasound images to determine leiomyoma size and level 2 FIGO type (submucous or other), and the linked electronic medical record abstracted for clinical features, including histopathological evidence of adenomyosis.ResultsOf the 370 subjects that met the study criteria, adenomyosis was identified via histopathology in 170 (45.9%). There was no difference in the adenomyosis prevalence with (47.1%) and without (43.0%) at least one submucous leiomyoma. Subgroup analysis of ultrasound images by an expert radiologist for the presence of adenomyosis demonstrated a positive predictive value of 54.0% and a negative predictive value of 43.4%.ConclusionsAdenomyosis was present in almost half of this AUB-L cohort undergoing hysterectomy and was equally prevalent in those with and without submucous leiomyomas as determined by sonographic evaluation. The imaging findings are in accord with prior investigators and demonstrate that 2-D ultrasound is insensitive to the presence of adenomyosis when the uterus is affected by leiomyomas. Further research is necessary to determine the impact of various adenomyosis phenotypes on the presence and severity of the symptom of HMB.
| S-EPMC10712893 | biostudies-literature
Project description:Although uterine leiomyomas are the most common benign uterine tumors in women, there is no effective therapy that can also preserve the uterus and maintain fertility. The work aimed to work was to discover a potential natural agent that has pharmacological activities on uterine leiomyomas with fewer adverse effects. We chose Rhus verniciflua Stokes (RVS) as a candidate after primary cytotoxicity testing, and analyzed the RVS components that showed pharmacological activity. Leiomyoma cells and myometrium cells were cultured from uterine tissues obtained from patients, and were treated with RVS at varying concentrations. RVS was cytotoxic in both leiomyoma and myometrium cells; however, the effects were more prominent in the leiomyoma cells. Among the bioactive components of RVS, fisetin showed significant pharmacological effects on leiomyoma cells. Fisetin showed excellent leiomyoma cell cytotoxicity and induced apoptotic cell death with cell cycle arrest. The apoptotic cell death appeared to involve not one specific pathway but multichannel pathways (intrinsic, extrinsic, MARK, and p53-mediated pathways), and autophagy. The multichannel apoptosis pathways were activated with a low concentration of fisetin (<IC20) and were more vigorously activated at high concentrations (>IC50). This is the first demonstration to show the pharmacological activities of fisetin on leiomyoma cells. These findings suggest that fisetin may be used for the prevention and treatment of uterine leiomyomas. Since fisetin can be obtained from plants, it may be a safe and effective alternative treatment for uterine leiomyomas.
| S-EPMC7224361 | biostudies-literature
Project description:ObjectiveIn the LIBERTY 1 and LIBERTY 2 placebo-controlled trials, once-daily relugolix combination therapy reduced menstrual blood loss volume and pain in women with heavy menstrual bleeding associated with uterine leiomyomas and was well tolerated, with preservation of bone mineral density (BMD) through 24 weeks. Here we report the long-term efficacy and safety of relugolix combination therapy treatment for up to 52 weeks.MethodsWomen with uterine leiomyoma-associated heavy menstrual bleeding who completed any treatment arm in either the LIBERTY 1 or LIBERTY 2 trial were eligible to enroll in a 28-week long-term extension study. All participants received once-daily relugolix combination therapy (40 mg relugolix, estradiol 1 mg, norethindrone acetate 0.5 mg) in the extension study. The primary efficacy endpoint was the proportion of women who achieved or maintained a menstrual blood loss volume of less than 80 mL and a 50% or greater reduction in menstrual blood loss volume from LIBERTY study baseline to the last 35 days of treatment (defined as responders ). Analyses were conducted for all three randomized treatment groups from pivotal studies.ResultsOverall, 477 women enrolled, 476 were treated, and 363 (76.1%) completed 52 weeks. Among patients treated with relugolix combination therapy through 52 weeks (n=163), sustained improvement in heavy menstrual bleeding was observed in 87.7% (responders). The least squares mean menstrual blood loss volume reduction was 89.9%, with 70.6% of patients achieving amenorrhea. At week 52, 59.0% of patients with anemia at baseline had improvements in hemoglobin concentration of greater than 2 g/dL. Distress due to uterine leiomyoma-associated symptoms measured by the BPD (Bleeding and Pelvic Discomfort) scale score was reduced by 51.3 points. Sustained reductions in uterine and uterine leiomyoma volume were observed. Bone mineral density was preserved through week 52.ConclusionImprovements in heavy menstrual bleeding and anemia and reduction of uterine leiomyoma-associated symptom burden were sustained through up to 52 weeks of treatment with relugolix combination therapy in women with uterine leiomyomas. No new safety concerns were identified, and BMD was maintained.Clinical trial registrationClinicalTrials.gov , NCT03049735; NCT03103087; NCT03412890.Funding sourceMyovant Sciences GmbH.
| S-EPMC9665945 | biostudies-literature
Project description: Not available
| S-EPMC3150866 | biostudies-literature
Project description:In order to ensure safe magnetic resonance-guided, high-intensity focused, ultrasound ablation of uterine leiomyomas, the ultrasound beam path should be free of intervening scar and bowel. Pre-treatment MRI of a 9-cm long and 7.7-cm wide leiomyomatous uterus in a 39-year-old woman with menorrhagia and abdominopelvic pain initially demonstrated a focused ultrasound treatment path without a bowel between the uterus and the abdominal wall. On the day of ablation, however, multiple loops of bowel were observed in the ultrasound beam path by MRI. Uterine repositioning was accomplished with a 76-mm donut vaginal pessary, which anteverted the fundus and successfully displaced the bowel. A vaginal pessary may aid in repositioning an axial or retroverted uterus to enable ablation of uterine leiomyomas.
| S-EPMC4864147 | biostudies-literature
Project description:Gene expression profiles of 10 uterine leiomyomas and their matched normal myometrium specimens were studied using Affymetrix GeneChip Human Genome U133 Plus 2.0 gene expression arrays. Four tumors displayed a codon 44 mutation, four carried a intron 1 mutation, and the remaining two displayed no MED12 mutation.
2011-08-26 | GSE30673 | GEO
Project description:PURPOSE:The preoperative distinction between uterine leiomyoma (LM) and leiomyosarcoma (LMS) is difficult, which may result in dissemination of an unexpected malignancy during surgery for a presumed benign lesion. An assay based on circulating tumor DNA (ctDNA) could help in the preoperative distinction between LM and LMS. This study addresses the feasibility of applying the two most frequently used approaches for detection of ctDNA: profiling of copy number alterations (CNAs) and point mutations in the plasma of patients with LM. PATIENTS AND METHODS:By shallow whole-genome sequencing, we prospectively examined whether LM-derived ctDNA could be detected in plasma specimens of 12 patients. Plasma levels of lactate dehydrogenase, a marker suggested for the distinction between LM and LMS by prior studies, were also determined. We also profiled 36 LM tumor specimens by exome sequencing to develop a panel for targeted detection of point mutations in ctDNA of patients with LM. RESULTS:We identified tumor-derived CNAs in the plasma DNA of 50% (six of 12) of patients with LM. The lactate dehydrogenase levels did not allow for an accurate distinction between patients with LM and patients with LMS. We identified only two recurrently mutated genes in LM tumors (MED12 and ACLY). CONCLUSION:Our results show that LMs do shed DNA into the circulation, which provides an opportunity for the development of ctDNA-based testing to distinguish LM from LMS. Although we could not design an LM-specific panel for ctDNA profiling, we propose that the detection of CNAs or point mutations in selected tumor suppressor genes in ctDNA may favor a diagnosis of LMS, since these genes are not affected in LM.
| S-EPMC7105159 | biostudies-literature