Mapping Human Uterine Disorders Through Single-Cell Transcriptomics

Cells, Journal Year: 2025, Volume and Issue: 14(3), P. 156 - 156

Published: Jan. 21, 2025

Disruptions in uterine tissue function contribute to disorders such as endometriosis, adenomyosis, endometrial cancer, and fibroids, which all significantly impact health fertility. Advances transcriptomics, particularly single-cell RNA sequencing, have revolutionized biological research by revealing the cellular heterogeneity molecular mechanisms underlying disease states. Single-cell sequencing spatial transcriptomics mapped myometrial landscapes, helped identify critical cell types, signaling pathways, phase-specific dynamics. Said transcriptomic technologies also identified stromal immune dysfunctions, fibroblast-to-myofibroblast transitions impaired macrophage activity, drive fibrosis, chronic inflammation, lesion persistence endometriosis. For scRNA-seq uncovered tumor microenvironmental complexities, identifying cancer-associated fibroblast subtypes profiles contributing progression therapeutic resistance. Similarly, studies on adenomyosis highlighted disrupted including Wnt VEGF, novel progenitor populations linked invasion neuroinflammation, while approaches characterized smooth muscle subpopulations elucidating their roles extracellular matrix remodeling pathways like ERK mTOR. Despite challenges scalability reproducibility, may potential applications biomarker discovery, target identification, personalized medicine gynecological disorders.

Language: Английский

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Genome-wide association analysis identified inflammatory mechanisms mediating the effects of lipid metabolism on endometrial carcinoma in situ

Journal of Chromatography B, Journal Year: 2025, Volume and Issue: 1258, P. 124601 - 124601

Published: April 17, 2025

Language: Английский

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Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 733, P. 150437 - 150437

Published: July 23, 2024

Language: Английский

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First-Line Lenvatinib Plus Pembrolizumab Versus Chemotherapy for Advanced Endometrial Cancer: A Randomized, Open-Label, Phase III Trial

Journal of Clinical Oncology, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 26, 2024

PURPOSE Lenvatinib plus pembrolizumab (len + pembro) significantly improved progression-free survival (PFS) and overall (OS) versus chemotherapy in previously treated advanced or recurrent endometrial cancer (aEC) the phase III Study 309/KEYNOTE-775. We report results from III, randomized, open-label European Network of Gynaecological Oncological Trial-en9/LEAP-001 study (ClinicalTrials.gov identifier: NCT03884101 ) that evaluated len pembro first-line aEC. METHODS Patients with stage to IV recurrent, radiographically apparent EC no previous disease progression ≥6 months after neo/adjuvant platinum-based were randomly assigned 1:1 lenvatinib 20 mg once daily 200 every 3 weeks paclitaxel 175 mg/m 2 carboplatin AUC 6 mg/mL/min weeks. Primary end points PFS OS, mismatch repair-proficient (pMMR) all-comers populations. Noninferiority was assessed for OS at final analysis (FA) (multiplicity-adjusted, one-sided nominal alpha, .0159; null hypothesis–tested hazard ratio [HR], 1.1). RESULTS Eight hundred forty-two patients pembro, n = 420 [pMMR population, 320]; chemotherapy, 422 322]). At FA (data cutoff, October 2, 2023), median (95% CI) pMMR population 9.6 (8.2 11.9) 10.2 (8.4 10.5) (hazard 0.99 [95% CI, 0.82 1.21]) among 12.5 (10.3 15.1) 10.4) (HR, 0.91 0.76 1.09]; descriptive analyses). Median 30.9 (25.4 37.7) 29.4 (26.2 35.4) 1.02 0.83 1.26]; noninferiority P .246, not statistically significant per multiplicity control strategy) 37.7 (32.2 43.6) 32.1 (27.2 35.7) 0.93 0.77 1.12]). Grade ≥3 treatment-related adverse events occurred 331/420 (79%) 274/411 (67%) patients. CONCLUSION First-line did meet prespecified statistical criteria

Language: Английский

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Predicting immunotherapy efficacy in endometrial cancer: focus on the tumor microenvironment

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Immunotherapy represents a groundbreaking therapeutic approach, based on the immune system’s intrinsic capacity to interfere with tumor progression, that opens horizons in treatment of endometrial cancer. However, clinical efficacy immunotherapy is hampered by development resistance patients. The multifactorial mechanism, encompassed genetic and epigenetic alterations cells modulating checkpoint molecules, resulted escaping surveillance. microenvironment can orchestrate an immunosuppressive milieu, attenuating response facilitating progression. To overcome immunotherapeutic cancer we must bring light mechanisms intricate interplay between neoplastic cells, host system, microenvironment. identification predictive biomarkers for innovative agents capable reversing pathways be developed. Our review summarizes accumulated data role their regulatory molecules underlying effects inhibitors, including therapy. Major question raise here – which group patients most favorable achieve durable cancer?

Language: Английский

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Assessment of Cyclin D1 Expression: Prognostic Value and Functional Insights in Endometrial Cancer: In Silico Study

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 890 - 890

Published: Jan. 22, 2025

Endometrial cancer (EC) is the sixth most common in women worldwide, with rising incidence, particularly economically developed countries where obesity and type 2 diabetes are prevalent risk factors. EC comprises various histological subtypes distinct behaviors: Type I tumors generally estrogen-driven favorable prognosis, while II hormone-independent, aggressive, associated poorer outcomes. Dysregulation of cell cycle, through cyclin-dependent kinases (CDKs) their regulators like Cyclin D1 (CCND1), plays a crucial role progression recurrence. overexpression often observed early stages endometrioid carcinoma complex hyperplasia, marking potential carcinogenic events, lower expression levels high-grade serous carcinoma. Although CDK inhibitors targeting D1/CDK4/6 complexes have shown therapeutic cancers such as breast lung, remains underexplored. This study integrates immunohistochemical evaluations patient samples data from The Cancer Genome Atlas (TCGA) to assess its prognostic significance across subtypes. By correlating molecular, histopathological, clinical outcomes, we aim clarify impact dysregulation on Our findings may inform more personalized approaches, for treatment-resistant forms EC.

Language: Английский

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Uterine Carcinosarcoma—A Retrospective Cohort Analysis from a Tertiary Centre on Epidemiology, Management Approach, Outcomes and Survival Patterns

Cancers, Journal Year: 2025, Volume and Issue: 17(4), P. 635 - 635

Published: Feb. 14, 2025

Uterine carcinosarcoma (UCS) refers to a rare high-grade aggressive epithelial non-endometrioid endometrial carcinoma, with tumour cells demonstrating epithelial-mesenchymal metaplastic transition and composed of both carcinomatous sarcomatous (homologous or heterologous) components. The aim this study was evaluate the epidemiology, management approach, outcomes survival patterns patients UCS. Seventy-seven cases UCS treated primary surgery in single tertiary centre underwent retrospective cohort analysis across ten-year period. Observational data on clinicopathological variables treatment pathways were reviewed independent risk factors for relapse mortality analysed. 5-year disease-free overall rates 52.10% 46.6%, respectively. Cervical stromal involvement independently related (HR = 6.26; 95%CI 1.82-21.59; p 0.004) 3.64; 1.42-9.38; 0.007), whilst component type recurrence only 3.62; 1.38-9.51; 0.009) after adjusting other pathological variables. No significant difference found when comparing performance pelvic lymph node dissection (p 0.803 0.192 respectively) administration adjuvant 0.546 0.627 respectively). Whilst our suggests an encouraging similarity compared literature, continues represent challenges-with paucity guidelines available. Data regarding molecular not systemically available cohort, more recent introduction which (alongside revision cancer staging) will undoubtedly provide improved therapeutic options future.

Language: Английский

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Genetic analysis of uterine lavage fluids to identify women at high risk of endometrial cancer

BMC Research Notes, Journal Year: 2025, Volume and Issue: 18(1)

Published: March 18, 2025

Abstract Objectives Endometrial cancer (EC) is the most common malignancy of female genital tract in developed countries, yet preventive screening remains unavailable, and diagnostic approaches are largely limited to symptomatic women. Despite advancements precision oncology, biology precancerous lesions less understood compared advanced disease. To address this gap, we conducted a prospective case-control study analysing uterine lavage fluid from women undergoing evaluation. The included 257 participants: 80 diagnosed with endometrial intraepithelial neoplasia (EIN), 89 early-stage EC, 88 healthy controls. Using targeted next-generation sequencing, examined genetic alterations 22 selected genes associated EC development. Results Our findings did not confirm direct association between specific mutations presence EIN or ( p = 0.501). Mutations were detected both cases controls, higher overall mutation burden observed suggesting potential background genomic unrelated In conclusion, while molecular profiling promising concept for non-invasive diagnosis, our results highlight significant challenges specificity. Further studies larger cohorts additional biomarkers necessary clarify its relevance clinical applicability.

Language: Английский

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Feasibility of deep learning-based super-resolution reconstruction for endometrial cancer T2-weighted imaging

Published: May 8, 2025

Background No study has assessed the application of deep learning (DL) networks in combination with more advanced super-resolution (SR) reconstruction for endometrial cancer (EC) MRI and influence this methods on myometrial invasion. We aimed to evaluate performance clinical value DL-based SR image quality improvement under-sampling accelerated EC T2WI. Methods Two sets T2WI were acquired 23 volunteers low (T2_LR) high (T2_HR) resolution, respectively. For 41 patients, T2_LR MultiVane (T2_MV) performed. T2_SR images reconstructed from through DL network. Image diagnostic accuracy evaluated by radiologists. Results volunteers, signal-to-noise ratio peak notably higher than those T2_HR, edge rise distance was lower (P < 0.005). sharpness, capsule delineation, overall quality, confidence T2_MV Compared T2_MV, scanning time reduced 61% (50s vs. 128s). had similar invasion Conclusions significantly improved uterus compared conventional iterative compressed sensing, saving ensuring accurate evaluation cancer.

Language: Английский

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Global trend of cervical cancer among women aged 55 and older from 2010 to 2019: An analysis by socio‐demographic index and geographic regions

Aging Medicine, Journal Year: 2024, Volume and Issue: 7(5), P. 614 - 635

Published: Oct. 1, 2024

Abstract Objective This study describes the 2010–2019 trend of cervical cancer (CC) in women over 55 by socio‐demographic index (SDI) and geographical regions. Methods We obtained data on CC annually from 2010 to 2019 Global Burden Disease Study (GBD) analyze incidence, death prevalence rates, disability‐adjusted life years (DALYs) associated with across different parameters such as global trend, age groups, SDI, continents, World Bank Regions, Health Organization (WHO) regions, GBD National territorial division. analysis covers 204 countries territories 1990 2019. Results There were 236,228 incidence cases worldwide 2019, which is a 1.27‐fold increase 2010. deaths also increased 169,304 reflecting 1.24‐fold increase. 769,925 representing 1.4‐fold rise. The number DALYs globally 3,835,979 Incidence, death, prevalence, DALY numbers all groups females 65–69 group experienced highest Middle SDI had numbers, while low showed increasing trends. Asia exhibited CC. Upper middle‐income decreases these rates except rate. Western Pacific Region declining rate Republic Kiribati numbers. Conclusion Based results, it clear that although epidemiological indicators decreasing, largest proportion decreasing related developing countries. But regions Africa have lower level development, sometimes show upward trends, shows worsening problem need for serious policies plans implement comprehensive vaccination, screening, promotion interventions. People's awareness necessary field better disease control.

Language: Английский

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