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The Morphologic and Molecular Heterogeneity of Fumarate Hydratase-deficient Leiomyomas: Integrative Molecular Profiling of Uterine Smooth Muscle Tumors With Histologic Feature Correlation.
Int J Gynecol Pathol
January 2025
Departments of Pathology.
The morphologic features of uterine smooth muscle tumors (USMTs) are subject to interobserver variability and are complicated by consideration of features of fumarate hydratase deficiency (FHd) and other morphologic subtypes, with difficult cases occasionally diagnosed as smooth muscle tumor of uncertain malignant potential (STUMP). We compare immunohistochemical findings and detailed morphologic analysis of 45 USMTs by 4 fellowship-trained gynecologic pathologists with comprehensive molecular analysis, focusing on FHd leiomyomas (n=15), compared to a variety of other USMTs with overlapping morphologic features, including 9 STUMPs, 8 usual-type leiomyomas (ULM), 11 apoplectic leiomyomas, and 2 leiomyomas with bizarre nuclei (LMBN). FHd leiomyomas, defined by immunohistochemical (IHC) loss of FH and/or 2SC accumulation, showed FH mutations and/or FH copy loss in all cases, with concurrent TP53 mutations in 2 tumors.
View Article and Find Full Text PDFGnRH Peptide Antagonist: Comparative Analysis of Chemistry and Formulation with Implications for Clinical Safety and Efficacy.
Pharmaceuticals (Basel)
December 2024
College of Pharmacy, University of Illinois, Chicago, IL 60612, USA.
Overexpression of the gonadotropin-releasing hormone receptor (GnRH-R) plays a vital role in the advancement of reproductive malignancies such as ovarian, endometrial, and prostate cancer. Peptidomimetic GnRH antagonists are a substantial therapeutic development, providing fast and reversible suppression of gonadotropins by directly blocking GnRH-R. Unlike typical GnRH agonists, these antagonists prevent the early hormonal flare, have a faster onset of action, and have a lower risk of cardiovascular problems.
View Article and Find Full Text PDFPromising candidate drug target genes for repurposing in cervical cancer: A bioinformatics-based approach.
Narra J
December 2024
Graduate School in Biomedical Sciences, Faculty of Medicine, Universitas Riau, Pekanbaru, Indonesia.
Cervical cancer is the fourth most common cancer among women globally, and studies have shown that genetic variants play a significant role in its development. A variety of germline and somatic mutations are associated with cervical cancer. However, genomic data derived from these mutations have not been extensively utilized for the development of repurposed drugs for cervical cancer.
View Article and Find Full Text PDFIn Vitro Effect of Estrogen and Progesterone on Cytogenetic Profile of Uterine Leiomyomas.
Int J Mol Sci
December 2024
D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, 199034 St. Petersburg, Russia.
In the present study, we aimed to investigate intratumoral karyotype diversity as well as the estrogen/progesterone effect on the cytogenetic profile of uterine leiomyomas (ULs). A total of 15 UL samples obtained from 15 patients were cultured in the media supplemented with estrogen and/or progesterone and without adding hormones. Conventional cytogenetic analysis of culture samples revealed clonal chromosomal abnormalities in 11 out of 15 ULs.
View Article and Find Full Text PDFHumanin alone and in combination with GnRHa therapy attenuates ovarian dysfunction induced by prepubertal cyclophosphamide chemotherapy in female mice.
Reprod Toxicol
January 2025
Reproductive Genetics Department, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, China. Electronic address:
Prepubertal chemotherapy induced ovarian damage poses a significant threat to female fertility, particularly following cyclophosphamide (CP) treatment. Humanin (HNG), a small molecule polypeptide encoded by mitochondrial DNA, has a variety of effects, this study aimed to investigate the protective effects of HNG and its combination with conventional Gonadotropin Releasing Hormone Agonist (GnRHa) on ovarian function in a CP-induced damage model. The 21-day-old C57BL/6 J female mice were randomly assigned to six groups: Control, CP model, HNG, HNG+CP, GnRHa+CP, and HNG+GnRHa+CP.
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