-
Nutrients Dec 2023Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs... (Review)
Review
Uterine fibroids are benign tumors that arise from the smooth muscle tissue of the uterus and are the most common tumors in women. Due to their high prevalence, costs for the health care system and the substantial impact on women's quality of life, they are a significant public health concern. Previous literature on the impact of diet on the occurrence, growth and symptoms of fibroids is limited. Recently, many papers have been written on this topic. A scoping review of PubMed and Cochrane databases was performed using the following keywords: uterine fibroids, antioxidants, diet, diet, vegetarian, vegetables, fruits, meat and soy foods, dairy products, tea, vitamin D, vitamin C, ascorbic acid. Preliminary research has shown a beneficial effect of vegetable and fruit consumption on the occurrence of fibroids. A relationship between hypovitaminosis D and an increased risk of fibroids has also been demonstrated. Studies on epigallocatechin gallate showed its apoptosis-promoting and antifibrinolytic effect in fibroid cells. Initial results are promising, but further randomized trials are needed to draw firm conclusions about the effects of diet and nutrients on uterine fibroids.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Vitamins; Diet; Vegetables; Ascorbic Acid
PubMed: 38068842
DOI: 10.3390/nu15234984 -
Nature Communications Dec 2023Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS...
Rhabdomyosarcomas (RMS) are pediatric mesenchymal-derived malignancies encompassing PAX3/7-FOXO1 Fusion Positive (FP)-RMS, and Fusion Negative (FN)-RMS with frequent RAS pathway mutations. RMS express the master myogenic transcription factor MYOD that, whilst essential for survival, cannot support differentiation. Here we discover SKP2, an oncogenic E3-ubiquitin ligase, as a critical pro-tumorigenic driver in FN-RMS. We show that SKP2 is overexpressed in RMS through the binding of MYOD to an intronic enhancer. SKP2 in FN-RMS promotes cell cycle progression and prevents differentiation by directly targeting p27 and p57, respectively. SKP2 depletion unlocks a partly MYOD-dependent myogenic transcriptional program and strongly affects stemness and tumorigenic features and prevents in vivo tumor growth. These effects are mirrored by the investigational NEDDylation inhibitor MLN4924. Results demonstrate a crucial crosstalk between transcriptional and post-translational mechanisms through the MYOD-SKP2 axis that contributes to tumorigenesis in FN-RMS. Finally, NEDDylation inhibition is identified as a potential therapeutic vulnerability in FN-RMS.
Topics: Humans; Carcinogenesis; Cell Line, Tumor; Rhabdomyosarcoma; Transcription Factors; Cell Transformation, Neoplastic; Cell Differentiation
PubMed: 38102140
DOI: 10.1038/s41467-023-44130-0 -
Japanese Journal of Clinical Oncology Nov 2023Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by... (Review)
Review
Alveolar soft part sarcoma is a rare neoplasm of uncertain histogenesis that belongs to a newly defined category of ultra-rare sarcomas. The neoplasm is characterized by a specific chromosomal translocation, der (17) t(X; 17)(p11.2;q25), that results in ASPSCR1-TFE3 gene fusion. The natural history of alveolar soft part sarcoma describes indolent behaviour with slow progression in deep soft tissues of the extremities, trunk and head/neck in adolescents and young adults. A high rate of detection of distant metastasis at presentation has been reported, and the most common metastatic sites in decreasing order of frequency are the lung, bone and brain. Complete surgical resection remains the standard treatment strategy, whereas radiotherapy is indicated for patients with inadequate surgical margins or unresectable tumours. Although alveolar soft part sarcoma is refractory to conventional doxorubicin-based chemotherapy, monotherapy or combination therapy using tyrosine kinase inhibitors and immune checkpoint inhibitors have provided antitumor activity and emerged as new treatment strategies. This article provides an overview of the current understanding of this ultra-rare sarcoma and recent advancements in treatments according to the clinical stage of alveolar soft part sarcoma.
Topics: Adolescent; Young Adult; Humans; Sarcoma, Alveolar Soft Part; Oncogene Proteins, Fusion; Soft Tissue Neoplasms; Translocation, Genetic; Combined Modality Therapy
PubMed: 37626447
DOI: 10.1093/jjco/hyad102 -
Journal of Molecular Endocrinology Nov 2023Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth....
Uterine fibroids (UFs) are benign tumors arising from the uterus, characterized by accumulation of abundant extracellular matrix (ECM) and sex steroid-dependent growth. Women with symptomatic UFs have reduced quality of life and decreased labor productivity. Among the driver gene mutations identified in UFs, mutations in MED12, a component of the cyclin-dependent kinase (CDK) Mediator module, are the most common and observed in 50-80% of UFs. They are gain-of-function mutations and are more frequently observed in Black women and commonly observed even in small UFs. MED12 mutation-positive UFs (MED12-UFs) often develop multiple rather than solitary and have distinct gene expression profiles, DNA methylomes, transcriptomes, and proteomes. Gene expressions related to ECM organization and collagen-rich ECM components are upregulated, and impaired Mediator kinase activity and dysregulation of Wnt/β-catenin signaling are identified in MED12-UFs. Clinically, the UF shrinking effect of gonadotropin-releasing hormone agonists and ulipristal acetate is dependent on the MED12 mutation status. Understanding of characteristics of MED12-UFs and functions of MED12 mutations for UF tumorigenesis may elucidate the pathophysiology of UFs, leading to the development of new therapeutic options in women with symptomatic UFs.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Mediator Complex; Leiomyoma; Transcription Factors; Mutation
PubMed: 37668348
DOI: 10.1530/JME-23-0039 -
Journal of Histotechnology Dec 2023
Review
Topics: Female; Humans; Leiomyoma; Uterine Neoplasms
PubMed: 37791571
DOI: 10.1080/01478885.2023.2265185 -
Frontiers in Cellular and Infection... 2023Dysbiosis of the female reproductive tract is closely associated with gynecologic diseases. Here, we aim to explore the association between dysbiosis in the genital... (Observational Study)
Observational Study
Dysbiosis of the female reproductive tract is closely associated with gynecologic diseases. Here, we aim to explore the association between dysbiosis in the genital tract and uterine fibroids (UFs) to further provide new insights into UF etiology. We present an observational study to profile vaginal and cervical microbiome from 29 women with UFs and 38 healthy women, and 125 samples were obtained and sequenced. By comparing the microbial profiles between different parts of the reproductive tract, there is no significant difference in microbial diversity between healthy subjects and UF patients. However, alpha diversity of UF patients was negatively correlated with the number of fibroids. Increased Firmicutes were observed in both the cervical and vaginal microbiome of UF patients at the phylum level. In differential analysis of relative abundance, some genera were shown to be significantly enriched (e.g., , , and ) and depleted (e.g., UCG-003 and ) in UF patients. Furthermore, the microbial co-occurrence networks of UF patients showed lower connectivity and complexity, suggesting reduced interactions and stability of the cervical and vaginal microbiota in UF patients. In summary, our findings revealed the perturbation of microbiome in the presence of UFs and a distinct pattern of characteristic vaginal and cervical microbiome involved in UFs, offering new options to further improve prevention and management strategies.
Topics: Female; Humans; Dysbiosis; Vagina; Microbiota; Leiomyoma; Microbial Consortia; Firmicutes
PubMed: 37743857
DOI: 10.3389/fcimb.2023.1196823 -
European Journal of Obstetrics,... Aug 2023Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The... (Review)
Review
BACKGROUND
Leiomyomas (fibroids), the most common benign solid tumours in females, originate from the myometrium and are associated with poor quality of life for patients. The current management of uterine leiomyomas mainly includes surgical interventions such as hysterectomy and myomectomy, either by laparoscopy or laparotomy, which have several complications and are not ideal for preserving fertility. Therefore, there is a need to develop or repurpose medical treatments that do not require surgical intervention.
OBJECTIVE
Many drugs are used to treat the symptoms associated with uterine fibroids. The main objective of this systematic review is to give an up-to-date account of potential pharmacological agents (non-surgical methods) for the management of uterine leiomyomas.
SEARCH STRATEGY
PubMed was searched for scientific and clinical literature using the keyword 'uterine fibroids' along with the drug names described in each section. For example, 'uterine fibroids' and 'ulipristal acetate' were the keywords used to search for literature on ulipristal acetate (UPA).
RESULTS
Various preclinical and clinical studies have shown that some drugs and herbal formulations exhibit activity in the management of uterine leiomyomas. Recent studies found that drugs such as UPA, elagolix, EC313, asoprisnol, nutritional supplements and herbal preparations were helpful in treating the symptoms associated with uterine leiomyomas.
CONCLUSION
Many drugs show efficacy in patients with symptomatic uterine fibroids. UPA is one of the most studied and prescribed medicines for uterine fibroids; however, its usage has been restricted due to a few recent incidences of hepatic toxicity. Herbal drugs and natural supplements have also shown promising effects on uterine fibroids. The synergistic effects of nutritional and herbal supplements have been reported in certain cases, and should be studied in detail. Further research is warranted to identify the mode of action of the drugs, and to determine the precise conditions that would explain the causes of toxicity in some patients.
Topics: Female; Humans; Uterine Neoplasms; Quality of Life; Leiomyoma; Uterine Myomectomy; Acetates
PubMed: 37385088
DOI: 10.1016/j.ejogrb.2023.06.021 -
Archives of Gynecology and Obstetrics Jul 2024
Topics: Humans; Female; Vulvar Neoplasms; Angiofibroma; Angiomyoma; Adult; Middle Aged
PubMed: 38483638
DOI: 10.1007/s00404-024-07450-0 -
BMJ Case Reports Jan 2024
Topics: Female; Humans; Rhabdomyosarcoma; Uterine Cervical Neoplasms; Uterus
PubMed: 38272523
DOI: 10.1136/bcr-2023-258853 -
Human Pathology May 2024Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification... (Review)
Review
Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents under the age of 20. The current World Health Organization (WHO) classification for soft tissue and bone tumors recognizes 4 distinct subtypes of RMS based on clinicopathological and molecular genetic features: embryonal, alveolar, spindle cell/sclerosing and pleomorphic subtypes. However, with the increased use of molecular techniques, the classification of rhabdomyosarcoma has been evolving rapidly. New subtypes such as osseus RMS harboring TFCP2/NCOA2 fusions or RMS arising in inflammatory rhabdomyoblastic tumor have been emerging within the last decade, adding to the complexity of diagnosing skeletal muscle tumors. This review article provides an overview of classically recognized distinctive subtypes as well as new, evolving subtypes and discusses important morphologic, immunophenotypic and molecular genetic features of each subtype including recommendations for a diagnostic approach of malignant skeletal muscle neoplasms.
Topics: Humans; Rhabdomyosarcoma; Immunohistochemistry; Biomarkers, Tumor; Soft Tissue Neoplasms; Predictive Value of Tests; Molecular Diagnostic Techniques; Phenotype; Genetic Predisposition to Disease; Child
PubMed: 38135061
DOI: 10.1016/j.humpath.2023.12.004