RESUMEN
Most bone tumors are metastatic. Breasts, lungs, kidneys, and thyroid are the primary sites most commonly involved in bone metastasis-type outcomes. This case study describes the involvement of a patient with a bone tumor located in the axial skeleton, initially in the sacral region. However, the primary site was undefined. Therefore, it was necessary to expand the investigation with immunohistochemistry, which demonstrated a metastatic tumor compatible with endometrioid adenocarcinoma. But even after examination, no active lesion was found in the endometrial region. The study was observational, descriptive, and aimed to discuss the importance of more specific investigative methods. In this context, immunohistochemistry stands out as an exquisite method capable of optimizing diagnosis, therapy, and consequently, prognosis.
Asunto(s)
Carcinoma Endometrioide , Neoplasias Endometriales , Sacro , Humanos , Femenino , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/secundario , Neoplasias Endometriales/patología , Sacro/patología , Neoplasias de la Columna Vertebral/secundario , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Persona de Mediana EdadRESUMEN
BACKGROUND: High-grade endometrial cancers (EAC) are aggressive tumors with a high risk of progression after treatment. As EAC may harbor mutations in the RAS/MAPK pathways, we evaluated the preclinical in vitro and in vivo efficacy of avutometinib, a RAF/MEK clamp, in combination with the focal adhesion kinase (FAK) inhibitors defactinib or VS-4718, against multiple primary EAC cell lines and xenografts. METHODS: Whole-exome sequencing (WES) was used to evaluate the genetic landscape of five primary EAC cell lines. The in vitro activity of avutometinib and defactinib as single agents and in combination was evaluated using cell viability, cell cycle, and cytotoxicity assays. Mechanistic studies were performed using Western blot assays while in vivo experiments were completed in UTE10 engrafted mice treated with either vehicle, avutometinib, VS-4718, or their combination through oral gavage. RESULTS: WES results demonstrated multiple EAC cell lines to harbor genetic derangements in the RAS/MAPK pathway including KRAS/PTEN/PIK3CA/BRAF/ARID1A, potentially sensitizing to FAK and RAF/MEK inhibition. Five out of five of the EAC cell lines demonstrated in vitro sensitivity to FAK and/or RAF/MEK inhibition. By Western blot assays, exposure of EAC cell lines to defactinib, avutometinib, and their combination demonstrated decreased phosphorylated FAK (p-FAK) as well as decreased p-MEK and p-ERK. In vivo the combination of avutometinib/VS-4718 demonstrated superior tumor growth inhibition compared to single-agent treatment and controls starting at Day 9 (p < 0.02 and p < 0.04) in UTE10 xenografts. CONCLUSIONS: Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts. These preclinical data support the potential clinical evaluation of this combination in high-grade EAC patients.
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Neoplasias Endometriales , Ensayos Antitumor por Modelo de Xenoinjerto , Femenino , Humanos , Animales , Ratones , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/patología , Neoplasias Endometriales/genética , Línea Celular Tumoral , Carcinoma Endometrioide/tratamiento farmacológico , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/metabolismo , Secuenciación del Exoma , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Proliferación Celular/efectos de los fármacos , Clasificación del Tumor , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Oxazepinas , Sulfonamidas , Pirazinas , Benzamidas , ImidazolesRESUMEN
Background: Since the seminal publication of the TCGA consortium in 2013, the molecular classification of endometrial cancer has been widely accepted as a new and powerful tool to better understand the natural history of this malignancy. Adoption of routine molecular classification around the world has been limited. We sought to demonstrate our initial experience in incorporating the four molecular subtypes for endometrioid carcinomas. Methods: This was a retrospective analysis at a single center in Portugal. Molecular classification was determined using immunohistochemical staining for MMR and p53 and Sanger Sequencing to determine POLE mutation status as per published PROMISE method. Descriptive statistics were reported. Results: 20 patients with endometrioid histology were included. Median age of the cohort was 64 years (range 45-76). Median Body Mass Index (kg/m2) was 29.81 (range 21.3-43.1). In terms of tumor grading, 16 (80%) of the endometrial carcinomas of the cohort were low-grade (either grade 1 or grade 2). 16 (80%) of the cases were FIGO stage I. Regarding the molecular classification the tumors were classified as: MMRd [n = 6 (30%)]; p53 abn [n = 2 (10%)]; NSMP (n = 10 (50%)), POLE ultramut [n = 2 (10%)]. Conclusion: Despite the small sample size, we were able to show that molecular classification is feasible. To our knowledge this is the first cohort of endometroid endometrial carcinomas fully characterized according to the TCGA classification in Portugal, from one single center.
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Biomarcadores de Tumor , Carcinoma Endometrioide , Neoplasias Endometriales , Humanos , Femenino , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/clasificación , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Portugal , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/clasificación , Biomarcadores de Tumor/genética , Mutación , Proteína p53 Supresora de Tumor/genética , PronósticoRESUMEN
BACKGROUND: Non-invasive risk stratification for patients with endometrial carcinoma (EC) is important for developing personalised treatment plans. Our study aimed to explore the ability of quantitative MRI parameters to predict the risk stratification of EC patients based on molecular classification. METHODS: Fifty-three patients with histologically proven EC who underwent pelvic MRI and surgical treatment at our hospital between January 2020 and August 2022 were assessed. The tumour volume (TV) and uterine volume (UV) were estimated with the ellipsoid formula and used to calculate the tumour volume ratio (TVR). The mean apparent diffusion coefficient (ADC) of the tumour was measured on a workstation. Quantitative MRI parameters were compared among different risk groups via unpaired Student's t-tests or Mann-Whitney's U-tests. RESULTS: The TV and TVR were significantly different between the low- and high-risk groups (p < 0.001), and cut-off values of 5342 mm3 and 0.055 allowed the differentiation of the high-risk group from the low-risk group, with 77% and 85% sensitivity and 78% and 78% specificity, respectively. There was a significant difference in the ADC between the two groups (p = 0.026), and a cut-off value of 0.65 × 10-3 mm2/s allowed differentiation of the risk groups, with 93% sensitivity and 39% specificity. CONCLUSIONS: Quantitative MRI parameters such as the TV, TVR and ADC may be helpful in preoperatively assessing the risk stratification of patients with EC based on molecular classification.
For patients with endometrial carcinoma (EC), it is important to assess the risk stratification based on molecular classification for developing treatment plans, but risk stratification is obtained most accurately from postoperative samples. We used non-invasive and easily accessible quantitative parameters of magnetic resonance imaging for preoperatively evaluating the risk stratification in these patients. We found that the quantitative parameters may be helpful in preoperatively assessing the risk stratification of patients with EC on the basis of molecular classification.
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Neoplasias Endometriales , Imagen por Resonancia Magnética , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/clasificación , Neoplasias Endometriales/diagnóstico por imagen , Persona de Mediana Edad , Medición de Riesgo/métodos , Imagen por Resonancia Magnética/métodos , Anciano , Pronóstico , Carga Tumoral , Adulto , Estudios Retrospectivos , Sensibilidad y EspecificidadRESUMEN
OBJECTIVES: The Ishikawa cell line is the most widely used model system for investigating implantation and endometrial cancer. Understanding the biology of this cell line is essential for developing effective interventional strategies. To gain a deeper understanding of its cellular protein profile, we extracted cellular proteins from Ishikawa cells and analyzed the peptides using mass spectrometry. Our goal was to create a proteomic resource specifically tailored for Ishikawa cells. This data set is of particular significance in the realm of targeted drug delivery. Liposomes are synthetic spherical vesicles composed of hydrophobic bilayer phospholipids and have received immense recognition as highly effective carriers for the delivery of pharmaceutical drugs and essential nutrients to the endometrium. Phosphatidylcholine and phosphatidylethanolamine are often combined to create functional liposomal systems. To discern any potential interfering effects originating from the liposome backbone, our investigation involved direct effects of phospholipid liposomes on endometrial epithelial cells. DATA DESCRIPTION: The data set includes peptide spectra derived from the intracellular proteomes of Ishikawa endometrial cancer cell isolates and their phospholipid-treated counterparts. Representing a proteome-wide profile, this dataset aims to contribute to a broader understanding of the physiology of endometrial epithelial cells. Proteomic analysis identified key proteins involved in the intricate regulation of cellular metabolism, cell cycle progression, and signaling. Between-group analysis revealed no differentially expressed proteins after adjusting for multiple testing using the applied thresholds (p-value < 0.05 and |logFC| > 1). Data are available via ProteomeXchange with identifier PXD050871.
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Neoplasias Endometriales , Liposomas , Proteómica , Femenino , Humanos , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Proteómica/métodos , Línea Celular Tumoral , Proteoma/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatidilcolinas/metabolismoRESUMEN
BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.
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Hiperplasia Endometrial , Neoplasias Endometriales , Preservación de la Fertilidad , Hormona Liberadora de Gonadotropina , Levonorgestrel , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/complicaciones , Neoplasias Endometriales/tratamiento farmacológico , Preservación de la Fertilidad/métodos , Embarazo , Levonorgestrel/administración & dosificación , Levonorgestrel/efectos adversos , Levonorgestrel/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/administración & dosificación , Dispositivos Intrauterinos Medicados , Resultado del Tratamiento , Adulto , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/administración & dosificación , Letrozol/administración & dosificación , Letrozol/uso terapéutico , China , Índice de EmbarazoRESUMEN
Obesity is a known driver of endometrial cancer. In this issue of the JCI, Gómez-Banoy and colleagues investigated a cohort of patients with advanced endometrial cancer treated with immune checkpoint inhibitors targeting the interaction between programmed cell death receptor-1 (PD-1) and its ligand (PD-L1). Notably, a BMI in the overweight or obese range was paradoxically associated with improved progression-free and overall survival. A second paradox emerged from CT analyses of visceral adipose tissue, viewed as an unhealthy fat depot in most other contexts, the quantity of which was also associated with improved treatment outcomes. Though visceral adiposity may have value as a biomarker to inform personalized treatment strategies, of even greater impact would be if a therapeutic strategy emerges from the future identification of adipose-derived mediators of this putative anticancer immune-priming effect.
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Neoplasias Endometriales , Grasa Intraabdominal , Humanos , Femenino , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/terapia , Neoplasias Endometriales/patología , Neoplasias Endometriales/tratamiento farmacológico , Grasa Intraabdominal/inmunología , Inmunoterapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Obesidad/inmunología , Obesidad/terapia , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunologíaRESUMEN
Neoadjuvant immune checkpoint blockade (ICB) has shown unprecedented activity in mismatch repair deficient (MMRd) colorectal cancers, but its effectiveness in MMRd endometrial cancer (EC) remains unknown. In this investigator-driven, phase I, feasibility study (NCT04262089), 10 women with MMRd EC of any grade, planned for primary surgery, received two cycles of neoadjuvant pembrolizumab (200 mg IV) every three weeks. A pathologic response (primary objective) was observed in 5/10 patients, with 2 patients showing a major pathologic response. No patient achieved a complete pathologic response. A partial radiologic response (secondary objective) was observed in 3/10 patients, 5/10 patients had stable disease and 2/10 patients were non-evaluable on magnetic resonance imaging. All patients completed treatment without severe toxicity (exploratory objective). At median duration of follow-up of 22.5 months, two non-responders experienced disease recurrence. In-depth analysis of the loco-regional and systemic immune response (predefined exploratory objective) showed that monoclonal T cell expansion significantly correlated with treatment response. Tumour-draining lymph nodes displayed clonal overlap with intra-tumoural T cell expansion. All pre-specified endpoints, efficacy in terms of pathologic response as primary endpoint, radiologic response as secondary outcome and safety and tolerability as exploratory endpoint, were reached. Neoadjuvant ICB with pembrolizumab proved safe and induced pathologic, radiologic, and immunologic responses in MMRd EC, warranting further exploration of extended neoadjuvant treatment.
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Anticuerpos Monoclonales Humanizados , Reparación de la Incompatibilidad de ADN , Neoplasias Endometriales , Inhibidores de Puntos de Control Inmunológico , Terapia Neoadyuvante , Humanos , Femenino , Neoplasias Endometriales/tratamiento farmacológico , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Neoplasias Endometriales/inmunología , Neoplasias Endometriales/diagnóstico por imagen , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Persona de Mediana Edad , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anciano , Adulto , Resultado del TratamientoRESUMEN
BACKGROUND: Yolk sac tumor (YST) is a highly malignant germ cell tumor, a majority of which originate from the gonads and are extremely rare from endometrium. CASE PRESENTATION: Here we present a case of a 42-year-old woman suffered from primary pure yolk sac tumor of the endometrium complicated with situs inversus totalis. The patient presented at our hospital with irregular vaginal bleeding. Imageological examination showed a space-occupying lesion in the cervix and the serum Alpha-fetoprotein (AFP) level was significantly high (more than 1210ng/ml). Then she underwent total hysterectomy, bilateral salpingo-oophorectomy and pelvic lymph node dissection. The subsequent postoperative pathological diagnosis was yolk sac tumor arising from the endometrium. Next, the patient was treated with 6 cycles of chemotherapy with Pingyangmycin, etoposide and cisplatin regimen and was alive without evidence of recurrence or distant metastases for 13 months. CONCLUSIONS: This rare disease needs to be differentiated from endometrial epithelial neoplasia and the significant increase in AFP is helpful for diagnosis. Combined with previous literature reports, comprehensive staging laparotomy or maximum cytoreductive surgery complemented by standard chemotherapy can usually achieve a good efficacy.
Asunto(s)
Tumor del Seno Endodérmico , Neoplasias Endometriales , Situs Inversus , Humanos , Femenino , Tumor del Seno Endodérmico/complicaciones , Tumor del Seno Endodérmico/diagnóstico , Tumor del Seno Endodérmico/patología , Adulto , Situs Inversus/complicaciones , Situs Inversus/diagnóstico , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , alfa-Fetoproteínas/análisis , Histerectomía/métodosRESUMEN
Single-cell RNA sequencing (scRNA-seq) technology has emerged as a powerful tool for dissecting cellular heterogeneity and understanding the intricate biology of diseases, including cancer. Endometrial cancer (EC) stands out as the most prevalent gynecological malignancy in Europe and the second most diagnosed worldwide, yet its cellular complexity remains poorly understood. In this review, we explore the contributions of scRNA-seq studies to shed light on the tumor cells and cellular landscape of EC. We discuss the diverse tumoral and microenvironmental populations identified through scRNA-seq, highlighting the implications for understanding disease progression. Furthermore, we address potential limitations inherent in scRNA-seq studies, such as technical biases and sample size constraints, emphasizing the need for larger-scale research encompassing a broader spectrum of EC histological subtypes. Notably, a significant proportion of scRNA-seq analyses have focused on primary endometrioid carcinoma tumors, underscoring the need to incorporate additional histological and aggressive types to comprehensively capture the heterogeneity of EC. By critically evaluating the current state of scRNA-seq research in EC, this review underscores the importance of advancing towards more comprehensive studies to accelerate our understanding of this complex disease.
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Neoplasias Endometriales , Análisis de la Célula Individual , Microambiente Tumoral , Humanos , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Femenino , Análisis de la Célula Individual/métodos , Microambiente Tumoral/genética , Células Epiteliales/metabolismo , Células Epiteliales/patología , Análisis de Secuencia de ARN , Animales , Biomarcadores de Tumor/genéticaRESUMEN
Studies have indicated that RAB17 expression levels are associated with tumor malignancy, and RAB17 is more highly expressed in endometrial cancer (EC) tissues than in peritumoral tissues. However, the roles and potential mechanisms of RAB17 in EC remain undefined. The present study confirmed that the expression of RAB17 facilitates EC progression by suppressing cellular ferroptosis-like alterations. Mechanistically, RAB17 attenuated ferroptosis in EC cells by inhibiting transferrin receptor (TFRC) protein expression in a ubiquitin proteasome-dependent manner. Because EC is a blood-deprived tumor with a poor energy supply, the relationship between RAB17 and hypoglycemia was investigated. RAB17 expression was increased in EC cells incubated in low-glucose medium. Moreover, low-glucose medium limited EC cell ferroptosis and promoted EC progression through the RAB17-TFRC axis. The in vitro results were corroborated by in vivo studies and clinical data. Overall, the present study revealed that increased RAB17 promotes the survival of EC cells during glucose deprivation by inhibiting the onset of TFRC-dependent ferroptosis.
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Progresión de la Enfermedad , Neoplasias Endometriales , Ferroptosis , Receptores de Transferrina , Proteínas de Unión al GTP rab , Animales , Femenino , Humanos , Ratones , Antígenos CD , Línea Celular Tumoral , Neoplasias Endometriales/patología , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/genética , Ferroptosis/genética , Glucosa/metabolismo , Ratones Desnudos , Proteínas de Unión al GTP rab/metabolismo , Proteínas de Unión al GTP rab/genética , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genéticaRESUMEN
Uterine cancer is the most common gynecologic malignancy in the United States, with endometrioid endometrial adenocarcinoma (EC) being the most common histologic sub-type. Considering the molecular classifications of EC, efforts have been made to identify additional biomarkers that can assist in diagnosis, prognosis, and individualized therapy. We sought to explore the relationship of Repressor Element 1 (RE1) silencing transcription factor (REST), which downregulates neuronal genes in non-neuronal tissue, along with matrix metalloproteinase-24 (MMP24) and EC. We analyzed the expression of REST and MMP24 in 31 cases of endometrial cancer and 16 controls. We then explored the baseline expression of REST and MMP24 in two EC cell lines (Ishikawa and HEC-1-A) compared to a benign cell line (t-HESC) and subsequently evaluated proliferation, migration, and invasion in the setting of loss of REST gene expression. REST and MMP24 expression were significantly lower in human EC samples compared to control samples. REST was highly expressed in EC cell lines, but decreasing REST gene expression increased proliferation (FC: 1.13X, p < 0.0001), migration (1.72X, p < 0.0001), and invasion (FC: 7.77X, p < 0.05) in Ishikawa cells, which are hallmarks of cancer progression and metastasis. These findings elicit a potential role for REST as a putative tumor suppressor in EC.
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Movimiento Celular , Proliferación Celular , Neoplasias Endometriales , Regulación Neoplásica de la Expresión Génica , Proteínas Represoras , Humanos , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Femenino , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Movimiento Celular/genética , Persona de Mediana Edad , Genes Supresores de Tumor , Anciano , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Invasividad NeoplásicaRESUMEN
BACKGROUND: The complex interplay between Sirtuin 1 (SIRT1) and FOXO3 in endometrial cancer (EC) remains understudied. This research aims to unravel the interactions of deacetylase SIRT1 and transcription factor FOXO3 in EC, focusing on their impact on mitophagy and hormone resistance. METHODS: High-throughput sequencing, cell experiments, and bioinformatics tools were employed to investigate the roles and interactions of SIRT1 and FOXO3 in EC. Co-immunoprecipitation (Co-IP) assay was used to assess the interaction between SIRT1 and FOXO3 in RL95-2 cells. Functional assays were used to assess cell viability, proliferation, migration, invasion, apoptosis, and the expression of related genes and proteins. A mouse model of EC was established to evaluate tumor growth and hormone resistance under different interventions. Immunohistochemistry and TUNEL assays were used to assess protein expression and apoptosis in tumor tissues. RESULTS: High-throughput transcriptome sequencing revealed a close association between SIRT1, FOXO3, and EC development. Co-IP showed a protein-protein interaction between SIRT1 and FOXO3. Overexpression of SIRT1 enhanced FOXO3 deacetylation and activity, promoting BNIP3 transcription and PINK1/Parkin-mediated mitophagy, which in turn promoted cell proliferation, migration, invasion, and inhibited apoptosis in vitro, as well as increased tumor growth and hormone resistance in vivo. These findings highlighted SIRT1 as an upstream regulator and potential therapeutic target in EC. CONCLUSION: This study reveals a novel molecular mechanism underlying the functional relevance of SIRT1 in regulating mitophagy and hormone resistance through the deacetylation of FOXO3 in EC, thereby providing valuable insights for new therapeutic strategies.
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Neoplasias Endometriales , Proteína Forkhead Box O3 , Mitofagia , Sirtuina 1 , Femenino , Proteína Forkhead Box O3/metabolismo , Proteína Forkhead Box O3/genética , Humanos , Mitofagia/genética , Sirtuina 1/metabolismo , Sirtuina 1/genética , Animales , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Línea Celular Tumoral , Ratones , Acetilación , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Apoptosis/genética , Movimiento Celular , Resistencia a Antineoplásicos/genéticaRESUMEN
We aimed to find new therapeutic targets related to Cancer Stem Cell alterations in recurrent patients from two TCGA cohorts: Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC). Raw sequencing data were downloaded from the TCGA database. Datasets containing RNA expression and Methylation files were directly downloaded from cBioportal. Variant Call Format files (VCFs) were downloaded from the GDC portal. Gene enrichment analysis was performed using GSEA (Gene Set Enrichment Analysis) software. Transcriptome profiling, coexpression co-occurrence, networks, and survival analyses were performed using cBioportal tools, while mutational analysis of patients was processed using UNIX scripts. We found that cancer stem cell transcription factors were highly expressed in Testicular Germ Cell Tumor (TGCT) and Uterine Corpus Endometrial Carcinoma (UCEC) cohorts, compared to the other 29 cancer cohorts in TCGA. Patients presented a poorer diagnosis when the genes (POU5F1, NANOG, SOX2, SALL4, ABCB1, ABCC1, and ABCG2) were altered. In UCEC cohorts, recurrent patients showed the ABCG2 potentially phosphorylated by the PIM1 kinase. In the TGCT cohort, genes ABCB1 and ABCG2 only appeared in the phosphonetwork in recurrent patients potentially phosphorylated by the same kinase, PIM1, but also by PRKACA. Our data indicate that PRKACA and PIM1 may modulate POU5F1 phosphorylation.
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Resistencia a Antineoplásicos , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Femenino , Neoplasias Testiculares/genética , Neoplasias Testiculares/tratamiento farmacológico , Masculino , Neoplasias de Células Germinales y Embrionarias/genética , Neoplasias de Células Germinales y Embrionarias/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Estudios de Cohortes , Neoplasias Uterinas/genética , Neoplasias Endometriales/genética , Neoplasias Endometriales/patología , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica/genéticaRESUMEN
BACKGROUND: Non-endometrioid endometrial carcinomas (NEEC) are characterized by their rarity and adverse prognoses. This study evaluates the outcomes of open versus minimally invasive surgery (MIS) in NEEC patients stratified by prognostic risks according to the 2020 ESGO-ESTRO-ESP risk classification guidelines. METHODS: A retrospective analysis was performed on 99 NEEC patients who underwent initial surgery at Fujian University Cancer Hospital. Patients were categorized into two groups: those undergoing MIS and those undergoing open surgery. We compared disease-free survival (DFS) and overall survival (OS) between these groups. Cox regression analysis was employed to identify risk factors for DFS, which were further validated via bootstrap statistical methods. RESULTS: The study included 31 patients in the MIS group and 68 in the open surgery group. The demographics and clinical characteristics such as age, body mass index, comorbidities, histological subtypes, and FIGO stage were similar between groups (P > 0.05). The MIS group experienced ten recurrences (1 vaginal, 2 lymph nodes, 7 distant metastases), whereas the open surgery group had seven recurrences (1 vaginal, 3 lymph nodes, 1 pelvis, 2 distant metastases), yielding recurrence rates of 10.3% versus 25.6% (P = 0.007). Besides lymphovascular space invasion (LVSI), surgical approach was also identified as an independent prognostic factor for DFS in high-risk patients (P = 0.037, 95% CI: 1.062-7.409). The constructed nomogram demonstrated a robust predictive capability with an area under the curve (AUC) of 0.767. Survival analysis for high- and intermediate-risk patients showed no significant differences in OS between the two groups (Phigh risk = 0.275; Pintermediate-risk = 0.201). However, high-risk patients in the MIS group exhibited significantly worse DFS (P = 0.001). CONCLUSION: This investigation is the inaugural study to assess the impact of surgical approaches on NEEC patients within the framework of the latest ESGO-ESTRO-ESP risk classifications. Although MIS may offer clinical advantages, it should be approached with caution in high-risk NEEC patients due to associated poorer DFS outcomes.
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Neoplasias Endometriales , Procedimientos Quirúrgicos Mínimamente Invasivos , Humanos , Femenino , Neoplasias Endometriales/cirugía , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Anciano , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Guías de Práctica Clínica como Asunto , Resultado del Tratamiento , Medición de Riesgo/métodos , Factores de Riesgo , Supervivencia sin EnfermedadRESUMEN
BACKGROUND: Endometrial cancer is one of the major gynecological cancers, with increasing incidence and mortality in the past decades. Emerging preclinical and clinical data have indicated its close association with obesity and dyslipidemia. Metabolism reprogramming has been considered as the hallmark of cancer, to satisfy the extensive need of nutrients and energy for survival and growth. Particularly, lipid metabolism reprogramming has aroused the researchers' interest in the field of cancer, including tumorigenesis, invasiveness, metastasis, therapeutic resistance and immunity modulation, etc. But the roles of lipid metabolism reprogramming in endometrial cancer have not been fully understood. This review has summarized how lipid metabolism reprogramming induces oncogenesis and progression of endometrial cancer, including the biological functions of aberrant lipid metabolism pathway and altered transcription regulation of lipid metabolism pathway. Besides, we proposed novel therapeutic strategies of targeting lipid metabolism pathway and concentrated on its potential of sensitizing immunotherapy and hormonal therapy, to further optimize the existing treatment modalities of patients with advanced/metastatic endometrial cancer. Moreover, we expect that targeting lipid metabolism plus hormone therapy may block the endometrial malignant transformation and enrich the preventative approaches of endometrial cancer. CONCLUSION: Lipid metabolism reprogramming plays an important role in tumor initiation and cancer progression of endometrial cancer. Targeting the core enzymes and transcriptional factors of lipid metabolism pathway alone or in combination with immunotherapy/hormone treatment is expected to decrease the tumor burden and provide promising treatment opportunity for patients with advanced/metastatic endometrial cancer.
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Neoplasias Endometriales , Metabolismo de los Lípidos , Humanos , Neoplasias Endometriales/metabolismo , Neoplasias Endometriales/patología , Neoplasias Endometriales/terapia , Femenino , Animales , Reprogramación Celular , Reprogramación MetabólicaRESUMEN
Background: In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. Methods: In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Conclusion: Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.
Asunto(s)
Neoplasias Endometriales , Hiperglucemia , Hipertensión , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/epidemiología , Persona de Mediana Edad , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Anciano , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Metástasis Linfática , Pronóstico , Adulto , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/complicaciones , Estudios RetrospectivosRESUMEN
OBJECTIVE: Endometrial cancer (EC) is the most common gynecological malignancy in high-income countries. In Taiwan, the incidence of EC increased from 1.69 in 1980 to 11.36 per 100,000 women/year in 2010. Therefore, we aimed to study the prognostic factors and survival of patients with EC in southern Taiwan. MATERIALS AND METHODS: This study included patients with EC who underwent hysterectomy-based surgery at our hospital between 2010 and 2020. The primary outcome was 5-year progression-free survival (PFS) and overall survival (OS) of patients diagnosed with EC. The secondary outcome was the prognostic factors associated with 5-year PFS and OS in patients with EC. We used the chi-square test to assess categorical variables and the independent t-test to assess continuous variables. The Kaplan-Meier method was used to estimate survival outcomes. Cox regression analysis was conducted to examine the factors associated with PFS and OS. RESULTS: A total of 133 patients were enrolled in this study. The mean age of the patients was 56.5 ± 10.71 years. The mean body mass index was 26.4 ± 5.21 kg/m2. The 5-year PFS and OS were 90.3% and 94.53%, respectively. In terms of PFS, endometrioid histology was linked to more favorable outcomes (hazard ratio [HR] = 0.02, 95% confidence interval [CI]:0.001-0.59), while lymph-vascular space invasion (LVSI) was associated with adverse results (HR = 9.11, 95% CI: 1.07-77.44). Initial analyses revealed no significant correlations between OS and various factors, including age, BMI, parity, DM, hypertension, age at last birth, and tumor grade. However, univariate analysis found grade 3 tumor differentiation, LVSI, and lymph node invasion associated with poorer OS. Laparoscopy was associated with better OS. Nevertheless, subsequent multivariate analysis did not reveal any factor significantly associated with OS. Most patients with EC (76.69%) underwent laparoscopic surgery. CONCLUSION: In conclusion, endometrioid histology was linked to more favorable PFS, while LVSI was related to adverse PFS. Our study did not identify any factors associated with OS. Two-thirds of the patients underwent minimally invasive surgery.
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Neoplasias Endometriales , Histerectomía , Humanos , Femenino , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Taiwán/epidemiología , Persona de Mediana Edad , Estudios Retrospectivos , Pronóstico , Histerectomía/estadística & datos numéricos , Anciano , Carcinoma Endometrioide/mortalidad , Carcinoma Endometrioide/patología , Carcinoma Endometrioide/cirugía , Estimación de Kaplan-Meier , Supervivencia sin Progresión , Tasa de Supervivencia , Estadificación de Neoplasias , Adulto , Modelos de Riesgos Proporcionales , Metástasis LinfáticaRESUMEN
OBJECTIVE: We present an unusual case of a small para-aortic lymphocele causing duodenal stenosis after lymphadenectomy and discuss its treatment. CASE REPORT: Our case involved a 57-year-old woman with endometrial cancer who underwent surgery, including para-aortic lymphadenectomy. On postoperative day 7, projectile vomiting occurred. Computed tomography (CT) revealed a small lymphocele in the dorsal duodenum, causing duodenal stenosis. Transpercutaneous and transduodenal puncture or surgical procedures were difficult because the cyst was too small. Per endoscopic and gastrointestinal series findings on the postoperative day 22, a liquid diet was presumed to be able to pass through the narrow portion. Hence, concentrated liquid food was administered orally; no vomiting occurred. At 2 months postoperatively, CT showed no lymphocele. CONCLUSION: Conservative treatment involving waiting for spontaneous lymphocele reduction with a concentrated fluid diet may be considered in such cases if fluid passage is confirmed with endoscopy and gastrointestinal series.
Asunto(s)
Neoplasias Endometriales , Escisión del Ganglio Linfático , Linfocele , Humanos , Femenino , Linfocele/etiología , Linfocele/cirugía , Linfocele/diagnóstico , Persona de Mediana Edad , Escisión del Ganglio Linfático/efectos adversos , Neoplasias Endometriales/cirugía , Obstrucción Duodenal/etiología , Obstrucción Duodenal/cirugía , Tomografía Computarizada por Rayos X , Complicaciones Posoperatorias/etiología , Constricción Patológica/etiologíaRESUMEN
AIM: Endometrial cancer (EC) is increasing in incidence in women across Aotearoa New Zealand as risk factors such as obesity and diabetes become more prevalent. In 2022, a Rapid Access Clinic (RAC) for hysteroscopy was implemented at Te Whatu Ora Counties Manukau District to increase early detection of EC. METHOD: Plan-Do-Study-Act (PDSA) cycles were used to test and implement RAC supported by a nurse pre-procedural phone consultation. Quantitative data was collected alongside patient experiences of the pre-procedural telephone call. RESULTS: A total of 207 women successfully completed RAC, which enabled one less visit to clinic per patient, subsequent travel cost savings (NZ$35,959) and a decrease in CO2 emissions (1,782kg). Lead time from first specialist appointment (FSA) to outpatient (OP) hysteroscopy, previously 25 days (SD: 21 days), was eliminated. Wait time from referral to provisional diagnosis increased from 26 days to 31 days; however, standard variation reduced from 30 days to 15 days. Clinician productivity increased by 25% per hysteroscopy session. Twenty-six out of 30 patients reported positive experiences of their pre-procedural RAC phone consultation. Twenty-seven out of 207 women were diagnosed with endometrial cancer from RAC. CONCLUSION: RAC are patient-centric and have demonstrated valuable benefits for both clinicians and women with a high suspicion of EC.