Obesity Contributes to Transformation of Myometrial Stem-Cell Niche to Leiomyoma via Inducing Oxidative Stress, DNA Damage, Proliferation, and Extracellular Matrix Deposition

Genes, Journal Year: 2023, Volume and Issue: 14(8), P. 1625 - 1625

Published: Aug. 15, 2023

Leiomyomas (fibroids) are monoclonal tumors in which myometrial stem cells (MSCs) turn tumorigenic after mutation, abnormal methylation, or aberrant signaling. Several factors contribute to metabolic dysfunction obesity, including cellular proliferation, oxidative stress, and DNA damage. The present study aims determine how adipocytes adipocyte-secreted affect changes MSCs a manner that promotes the growth of uterine leiomyomas. Myometrial were isolated from uteri patients by fluorescence-activated cell sorting (FACS) using CD44/Stro1 antibodies. Enzyme-linked immunosorbent assay (ELISA), Western blot, immunocytochemistry assays performed on human (SW872) co-cultured with treated leptin adiponectin examine effects extracellular matrix (ECM) deposition, damage, Co-culture SW872 increased MSC proliferation compared culture alone, according 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) results. expressions PCNA COL1A significantly co-culture. In addition, expression these markers was treatment decreased MSCs. Wnt/β-catenin TGF-β/SMAD signaling pathways promote ECM deposition Wnt4, β-catenin, TGFβ3, pSMAD2/3 when adipocytes. We found co-culture resulted NOX4 expression, reactive oxygen species production, γ-H2AX expression. Leptin acts binding its receptor (LEP-R), leading signal transduction, resulting transcription genes involved angiogenesis, glycolysis. MSCs, LEP-R, pSTAT3/STAT3, pERK1/2/ERK/12. Based above results, we suggest obesity may mediate initiation tumorigenesis,

Language: Английский

---

The adiposity of CRLM before targeted therapy initiation may serve as a marker to distinguish KRAS mutation status：A retrospective study

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: March 28, 2024

Abstract OBJECTIVE This study aimed to explore the correlation between MRI-related parameters and Kirsten rat sarcoma viral oncogene (KRAS) gene mutation status in colorectal cancer liver metastases (CRLM) prior initiating targeted therapy. METHODS retrospective enrolled 118 patients diagnosed with metastases, each presenting up three lesions of largest diameter, all underwent testing for KRAS mutations. Patients were categorized into two groups: mutant (+) group (53 patients, 119 lesions) wild-type (-) (65 155 lesions). Normality continuous variables was assessed using Kolmogorov-Smirnov test, while Mann-Whitney U test or T employed comparing variables, Chi-square categorical variables. Variables exhibiting significant differences (p < 0.05) subjected multivariate logistic regression identify independent factors construct predictive models. Model performance through receiver operating characteristic curve (ROC), area under (AUC) its 95% confidence interval (CI) calculated. RESULTS The T2-SI mean higher KRAS(+) compared KRAS(-) (0.91 ± 0.30 vs 0.87 0.39, p 0.001). Conversely, T2FS-SI significantly lower (0.80 0.27 1.02 0.65, Additionally, proportion a well-defined boundary notably (84.9% 65.2%, = 0.011). ROC analysis demonstrated that model (Y 0.890 + 0.878 * Boundary 5.955 − 5.667 ) yielded an AUC value 0.745 (95% CI: 0.688–0.802) predicting mutational gene. CONCLUSION In our study, , clear tumor boundaries CRLM therapy associated mutations.This implies adiposity before initiation may serve as marker distinguish status.

Language: Английский

---

Detection of Fat Cells in Uterine Scars During Normal Pregnancy and with Placenta Accreta Spectrum

Journal of Anatomy and Histopathology, Journal Year: 2023, Volume and Issue: 12(3), P. 57 - 64

Published: Oct. 6, 2023

The aim was to investigate the presence of fat cells (adipocytes) using morphological methods in uterus women without signs scarring, with well–off scars after cesarean section (CS), as well a group patients different variants atypical placentation. Material and methods. A retrospective histological immunohistochemical study uterine wall material obtained during abdominal delivery normal pregnancy previous CS medical history (group 1, n=10), anamnesis scar 2, n=23) performed, complicated by ingrowth placental villi 3, n=22). Results . In uteroplacental region, component found all three groups. No adipocytes were 1 (0%). fields sizes 19 cases out 23 studied (83%) only zone: serosa 40%, perivascular zone 28%, among muscle bundles 15%. 3rd into zone, “hernia” thinned detected 68% cases. adipocytic this 86% (19 22). Localization observed (56%), (25%) (6%). outside tissue. Conclusion An identified, undoubtedly associated traumatic damage wall. What are relationships between tissue its predisposition pathology is unknown requires further research.

Language: Английский

---