keyword
https://read.qxmd.com/read/38354856/loss-of-mitochondrial-pyruvate-carrier-1-supports-proline-dependent-proliferation-and-collagen-biosynthesis-in-ovarian-cancer
#21
JOURNAL ARTICLE
M R Farook, Z Croxford, S Morgan, A D Horlock, A Holt, A Rees, B J Jenkins, C Tse, E Stanton, D M Davies, C A Thornton, N Jones, I M Sheldon, E E Vincent, J G Cronin
The pyruvate transporter MPC1 (mitochondrial pyruvate carrier 1) acts as a tumour-suppressor, loss of which correlates with a pro-tumorigenic phenotype and poor survival in several tumour types. In high-grade serous ovarian cancers (HGSOC), patients display copy number loss of MPC1 in around 78% of cases and reduced MPC1 mRNA expression. To explore the metabolic effect of reduced expression, we demonstrate that depleting MPC1 in HGSOC cell lines drives expression of key proline biosynthetic genes; PYCR1, PYCR2 and PYCR3, and biosynthesis of proline...
February 12, 2024: Molecular Metabolism
https://read.qxmd.com/read/38352443/myc-is-sufficient-to-generate-mid-life-high-grade-serous-ovarian-and-uterine-serous-carcinomas-in-a-p53-r270h-mouse-model
#22
Alexandra Blackman, Amy C Rees, Robert R Bowers, Christian M Jones, Silvia G Vaena, Madison A Clark, Shelby Carter, Evan D Villamor, Della Evans, Anthony J Emanuel, George Fullbright, David T Long, Laura Spruill, Martin J Romeo, Kristi L Helke, Joe R Delaney
Genetically engineered mouse models (GEMM) have fundamentally changed how ovarian cancer etiology, early detection, and treatment is understood. However, previous GEMMs of high-grade serous ovarian cancer (HGSOC) have had to utilize genetics rarely or never found in human HGSOC to yield ovarian cancer within the lifespan of a mouse. MYC , an oncogene, is amongst the most amplified genes in HGSOC, but it has not previously been utilized to drive HGSOC GEMMs. We coupled Myc and dominant negative mutant p53-R270H with a fallopian tube epithelium-specific promoter Ovgp1 to generate a new GEMM of HGSOC...
January 29, 2024: bioRxiv
https://read.qxmd.com/read/38346978/residual-antxr1-myofibroblasts-after-chemotherapy-inhibit-anti-tumor-immunity-via-yap1-signaling-pathway
#23
JOURNAL ARTICLE
Monika Licaj, Rana Mhaidly, Yann Kieffer, Hugo Croizer, Claire Bonneau, Arnaud Meng, Lounes Djerroudi, Kevin Mujangi-Ebeka, Hocine R Hocine, Brigitte Bourachot, Ilaria Magagna, Renaud Leclere, Lea Guyonnet, Mylene Bohec, Coralie Guérin, Sylvain Baulande, Maud Kamal, Christophe Le Tourneau, Fabrice Lecuru, Véronique Becette, Roman Rouzier, Anne Vincent-Salomon, Geraldine Gentric, Fatima Mechta-Grigoriou
Although cancer-associated fibroblast (CAF) heterogeneity is well-established, the impact of chemotherapy on CAF populations remains poorly understood. Here we address this question in high-grade serous ovarian cancer (HGSOC), in which we previously identified 4 CAF populations. While the global content in stroma increases in HGSOC after chemotherapy, the proportion of FAP+ CAF (also called CAF-S1) decreases. Still, maintenance of high residual CAF-S1 content after chemotherapy is associated with reduced CD8+ T lymphocyte density and poor patient prognosis, emphasizing the importance of CAF-S1 reduction upon treatment...
February 12, 2024: Nature Communications
https://read.qxmd.com/read/38342715/mri-based-radiomics-model-to-preoperatively-predict-mesenchymal-transition-subtype-in-high-grade-serous-ovarian-cancer
#24
JOURNAL ARTICLE
Z Lin, H Ge, Q Guo, J Ren, W Gu, J Lu, Y Zhong, J Qiang, J Gong, H Li
AIM: To develop a magnetic resonance imaging (MRI)-based radiomics model for the preoperative identification of mesenchymal transition (MT) subtype in high-grade serous ovarian cancer (HGSOC). MATERIALS AND METHODS: One hundred and eighty-nine patients with histopathologically confirmed HGSOC were enrolled retrospectively. Among the included patients, 55 patients were determined as the MT subtype and the remaining 134 were non-MT subtype. After extracting a total of 204 features from T2-weighted imaging (T2WI) and contrast-enhanced (CE)-T1WI images, the Mann-Whitney U-test, Spearman correlation test, and Boruta algorithm were adopted to select the optimal feature set...
February 1, 2024: Clinical Radiology
https://read.qxmd.com/read/38293174/impact-of-spatial-clustering-of-cytotoxic-and-tumor-infiltrating-lymphocytes-on-overall-survival-in-women-with-high-grade-serous-ovarian-cancer
#25
Alex C Soupir, Mary K Townsend, Cassandra A Hathaway, Jonathan Nguyen, Carlos Moran Segura, Daryoush Saeed-Vafa, Oscar E Ospina, Lauren C Peres, Jose R Conejo-Garcia, Kathryn L Terry, Shelley S Tworoger, Brooke L Fridley
BACKGROUND: Studies have shown that tumor infiltrating lymphocyte (TILs) abundance is associated with overall survival in patients with high-grade serous ovarian cancer (HGSOC); however, the role of the spatial contexture and organization of TILs is less clear. METHODS: We evaluated the association between spatial architecture of T cells and survival in women with HGSOC from three large epidemiological studies in which tumors were analyzed by multiplex immunofluorescence (N = 433)...
January 17, 2024: medRxiv
https://read.qxmd.com/read/38290413/cd137-tumor-infiltrating-lymphocytes-predicts-ovarian-cancer-survival
#26
JOURNAL ARTICLE
Elizabeth A Tubridy, Monika A Eiva, Fang Liu, Dalia K Omran, Stefan Gysler, Erica G Brown, Allison G Roy, Yuyan Zeng, Jinhee Oh, Quy Cao, Sarah B Gitto, Daniel J Powell
OBJECTIVE: Ovarian cancer (OC) is the leading cause of death from gynecologic malignancy in the United States, and biomarkers of patient outcomes are limited. Data using immunohistochemical (IHC) analysis are mixed regarding whether and which tumor infiltrating lymphocytes (TILs) impact survival, and IHC does not adequately quantify rare cell populations, including CD137+ (4-1BB) tumor-reactive TILs. Our study investigates if a higher percentage of CD3+ CD137+ TILs is associated with improved overall survival (OS) in OC...
January 29, 2024: Gynecologic Oncology
https://read.qxmd.com/read/38287874/inhibition-of-palmitoyltransferase-zdhhc12-sensitizes-ovarian-cancer-cells-to-cisplatin-through-ros-mediated-mechanisms
#27
JOURNAL ARTICLE
Xining Zhang, Xingming Liao, Min Wang, Jiao Liu, Jiaxin Han, Dong An, Tiezheng Zheng, Xuefei Wang, Hailing Cheng, Pixu Liu
Platinum-based therapies have revolutionized the treatment of high-grade serous ovarian cancer (HGSOC). However, high rates of disease recurrence and progression remain a major clinical concern. Impaired mitochondrial function and dysregulated reactive oxygen species (ROS), hallmarks of cancer, hold potential as therapeutic targets for selectively sensitizing cisplatin treatment. Here, we uncover an oncogenic role of the palmitoyltransferase ZDHHC12 in regulating mitochondrial function and ROS homeostasis in HGSOC cells...
January 29, 2024: Cancer Science
https://read.qxmd.com/read/38282155/mir-451a-suppresses-the-proliferation-and-migration-of-high-grade-serous-ovarian-cancer-by-targeting-rab5a-through-the-ras-raf-mek-erk-pathway
#28
JOURNAL ARTICLE
Shujie Liu, Kun Wang, Zhendan Zhao, Yu Pang, Fang Liu, Pengling Wang, Zhiling Wang, Xingsheng Yang
BACKGROUND: Ovarian cancer is one of the most common cancers in women. Profiles changes of microRNAs (miRNAs) are closely linked to malignant tumors. In the present study, we investigated expression of miR-451a in high-grade serous ovarian cancer (HGSOC). We also investigated the potential pathological roles and the likely mechanism of miR-451a in the development of HGSOC using animal models and cell lines. METHODS: Using bioinformatics techniques and a real-time PCR, we analyzed differently expressed miRNAs in HGSOC compared to normal tissue...
January 2024: Journal of Gene Medicine
https://read.qxmd.com/read/38275400/high-grade-serous-ovarian-cancer-a-risk-factor-puzzle-and-screening-fugitive
#29
REVIEW
Jacek Wilczyński, Edyta Paradowska, Miłosz Wilczyński
High-grade serous ovarian cancer (HGSOC) is the most lethal tumor of the female genital tract. Despite extensive studies and the identification of some precursor lesions like serous tubal intraepithelial cancer (STIC) or the deviated mutational status of the patients ( BRCA germinal mutation), the pathophysiology of HGSOC and the existence of particular risk factors is still a puzzle. Moreover, a lack of screening programs results in delayed diagnosis, which is accompanied by a secondary chemo-resistance of the tumor and usually results in a high recurrence rate after the primary therapy...
January 19, 2024: Biomedicines
https://read.qxmd.com/read/38262243/5-hydroxymethylcytosine-signals-in-serum-are-a-predictor-of-chemoresistance-in-high-grade-serous-ovarian-cancer
#30
JOURNAL ARTICLE
Melanie Weigert, Xiao-Long Cui, Diana West-Szymanski, Xianbin Yu, Agnes Julia Bilecz, Zhou Zhang, Rohin Dhir, Mia Kehoe, Wei Zhang, Chuan He, Ernst Lengyel
OBJECTIVE: The genome-wide profiling of 5-hydroxymethylcytosines (5hmC) on circulating cell-free DNA (cfDNA) has revealed promising biomarkers for various diseases. The purpose of this study was to investigate 5hmC signals in serum cfDNA and identify novel predictive biomarkers for the development of chemoresistance in high-grade serous ovarian cancer (HGSOC). We hypothesized that 5hmC profiles in cfDNA reflect the development of chemoresistance and elucidate pathways that may drive chemoresistance in HGSOC...
January 22, 2024: Gynecologic Oncology
https://read.qxmd.com/read/38255960/human-fallopian-tube-derived-organoids-with-tp53-and-rad51d-mutations-recapitulate-an-early-stage-high-grade-serous-ovarian-cancer-phenotype-in-vitro
#31
JOURNAL ARTICLE
Yilin Dai, Jing Xu, Xiaofeng Gong, Jinsong Wei, Yi Gao, Ranran Chai, Chong Lu, Bing Zhao, Yu Kang
RAD51D mutations have been implicated in the transformation of normal fallopian tube epithelial (FTE) cells into high-grade serous ovarian cancer (HGSOC), one of the most prevalent and aggressive gynecologic malignancies. Currently, no suitable model exists to elucidate the role of RAD51D in disease initiation and progression. Here, we established organoids from primary human FTE and introduced TP53 as well as RAD51D knockdown to enable the exploration of their mutational impact on FTE lesion generation. We observed that TP53 deletion rescued the adverse effects of RAD51D deletion on the proliferation, stemness, senescence, and apoptosis of FTE organoids...
January 10, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38255835/differential-microrna-expression-analysis-in-patients-with-hpv-infected-ovarian-neoplasms
#32
JOURNAL ARTICLE
Dariusz Jarych, Damian Mikulski, Miłosz Wilczyński, Jacek R Wilczyński, Katarzyna D Kania, Daria Haręża, Andrzej Malinowski, Ewelina Perdas, Mateusz Nowak, Edyta Paradowska
This study aimed to identify microRNAs (miRNAs) whose expression levels are altered by high-risk human papillomavirus (HR-HPV) infection in women with epithelial ovarian neoplasms. MiRNA expression was quantified by real-time polymerase chain reaction, while HR-HPV DNA was quantified using digital-droplet PCR. Analysis of 11 miRNAs demonstrated significantly lower hsa-miR-25-5p expression in HPV-infected compared to uninfected ovarian tissues ( p = 0.0405), while differences in miRNA expression in corresponding serum were statistically insignificant...
January 7, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38248100/prediction-of-chemoresistance-how-preclinical-data-could-help-to-modify-therapeutic-strategy-in-high-grade-serous-ovarian-cancer
#33
REVIEW
Jacek Wilczyński, Edyta Paradowska, Justyna Wilczyńska, Miłosz Wilczyński
High-grade serous ovarian cancer (HGSOC) is one of the most lethal tumors generally and the most fatal cancer of the female genital tract. The approved standard therapy consists of surgical cytoreduction and platinum/taxane-based chemotherapy, and of targeted therapy in selected patients. The main therapeutic problem is chemoresistance of recurrent and metastatic HGSOC tumors which results in low survival in the group of FIGO III/IV. Therefore, the prediction and monitoring of chemoresistance seems to be of utmost importance for the improvement of HGSOC management...
December 29, 2023: Current Oncology
https://read.qxmd.com/read/38241710/akt1-interacts-with-dhx9-to-mitigate-r-loop-induced-replication-stress-in-ovarian-cancer
#34
JOURNAL ARTICLE
Tzu-Ting Huang, Chih-Yuan Chiang, Jayakumar R Nair, Kelli M Wilson, Ken Cheng, Jung-Min Lee
PARP inhibitor (PARPi)-resistant BRCA mutant (BRCAm) high-grade serous ovarian cancer (HGSOC) represents a new clinical challenge with unmet therapeutic needs. Here, we performed a quantitative high-throughput drug combination screen that identified the combination of an ATR inhibitor (ATRi) and an AKT inhibitor (AKTi) as an effective treatment strategy for both PARPi-sensitive and PARPi-resistant BRCAm HGSOC. The ATRi and AKTi combination induced DNA damage and R-loop-mediated replication stress (RS). Mechanistically, the kinase domain of AKT1 directly interacted with DHX9 and facilitated recruitment of DHX9 to R-loops...
January 19, 2024: Cancer Research
https://read.qxmd.com/read/38226451/altered-tumor-signature-and-t-cell-profile-after-chemotherapy-reveal-new-therapeutic-opportunities-in-high-grade-serous-ovarian-carcinoma
#35
JOURNAL ARTICLE
Huiram Kang, Sohyun Hwang, Haeyoun Kang, Areum Jo, Ji Min Lee, Jung Kyoon Choi, Hee Jung An, Hae-Ock Lee
Chemotherapy combined with debulking surgery is the standard treatment protocol for high-grade serous ovarian carcinoma (HGSOC). Nonetheless, a significant number of patients encounter relapse due to the development of chemotherapy resistance. To better understand and address this resistance, we conducted a comprehensive study investigating the transcriptional alterations at the single-cell resolution in tissue samples from patients with HGSOC, using single-cell RNA sequencing and T-cell receptor sequencing techniques...
January 16, 2024: Cancer Science
https://read.qxmd.com/read/38225339/ascites-exosomal-lncrna-plade-enhances-platinum-sensitivity-by-inducing-r-loops-in-ovarian-cancer
#36
JOURNAL ARTICLE
Hanyuan Liu, Sisi Deng, Xuelin Yao, Yi Liu, Lili Qian, Yingying Wang, Tianjiao Zhang, Ge Shan, Liang Chen, Ying Zhou
Cisplatin resistance is a major cause of therapeutic failure in patients with high-grade serous ovarian cancer (HGSOC). Long noncoding RNAs (lncRNAs) have emerged as key regulators of human cancers; however, their modes of action in HGSOC remain largely unknown. Here, we provide evidence to demonstrate that lncRNA Platinum sensitivity-related LncRNA from Ascites-Derived Exosomes (PLADE) transmitted by ascites exosomes enhance platinum sensitivity in HGSOC. PLADE exhibited significantly decreased expression in ascites exosomes and tumor tissues, as well as in the corresponding metastatic tumors from patients with HGSOC cisplatin-resistance...
January 15, 2024: Oncogene
https://read.qxmd.com/read/38219610/the-gustave-roussy-immune-score-as-a-novel-scoring-system-for-predicting-platinum-resistance-in-advanced-high-grade-serous-ovarian-cancer
#37
JOURNAL ARTICLE
Xianglin Nie, Ting Xu, Lin Zhang, Wenjun Cheng
OBJECTIVE: This study was designed to investigate the relationship between the Gustave-Roussy immune score (GRIm-score) and platinum resistance in patients with advanced high-grade serous ovarian cancer (HGSOC). METHODS: We conducted a retrospective study of patients diagnosed with advanced HGSOC between January 2017 and December 2020. A nomogram was developed to predict the risk of platinum resistance. Receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA) were used to validate the nomogram...
January 12, 2024: European Journal of Obstetrics, Gynecology, and Reproductive Biology
https://read.qxmd.com/read/38214360/circ_0070203-promotes-epithelial-mesenchymal-transition-in-ovarian-serous-cystadenocarcinoma-through-mir-370-3p-tgf%C3%AE-r2-axis
#38
JOURNAL ARTICLE
Qiong Tang, Huiting Wen, Haoyue Hu, Xiaoli Chen, Shuxiu Xu, Li Fan, Longyang Liu, Jing Li
INTRODUCTION: Circular RNAs (circRNAs) are important biological molecules associated with the pathogenesis of multiple cancers. OBJECTIVE: This work aimed to investigate the function and molecular mechanism of circ_0070203 in high-grade serous ovarian cystadenocarcinoma (HGSOC). METHODS: circRNA microarray was conducted to detect the circ_0070203 expression in HGSOC tissues. Bioinformatics analysis was used to find the binding sites between circ_0070203, miR- 370-3p and TGFβR2...
2024: Recent Patents on Anti-cancer Drug Discovery
https://read.qxmd.com/read/38211842/aldh1a3-contributes-to-tumorigenesis-in-high-grade-serous-ovarian-cancer-by-epigenetic-modification
#39
JOURNAL ARTICLE
Jiazhen Huang, Ying Tang, Yibing Li, Wei Wei, Fuli Kang, Shuang Tan, Lin Lin, Xiaohang Lu, Heng Wei, Ning Wang
High-grade serous ovarian cancer (HGSOC) is the most lethal histotype of ovarian cancer due to its unspecific symptoms in part. ALDH1A3 (aldehyde dehydrogenase 1 family member A3) is a key enzyme for acetyl-CoA production involving aggressive behaviors of cancers. However, ALDH1A3's effects and molecular mechanisms in HGSOC remain to be clarified. Using RNA-seq and publicly available datasets, ALDH1A3 was found to be highly expressed in HGSOC, and associated with poor survival. Knockdown of ALDH1A3 prevented HGSOC tumorigenesis and enhanced cell sensitivity to paclitaxel or cisplatin...
January 9, 2024: Cellular Signalling
https://read.qxmd.com/read/38201589/relapsed-ovarian-cancer-patients-with-ascites-and-or-pleural-effusion-still-benefit-from-treatment-a-real-life-study
#40
JOURNAL ARTICLE
Mariana Rebordão-Pires, Marta F Estrada, António Gomes, Filipa Silva, Carlota Baptista, Maria João Ramos, Ana Fortuna, Pedro Simões, Gabriela Sousa, Ana Marreiros, Rita Fior
(1) Background: Relapsed HGSOC with ascites and/or pleural effusion is a poor-prognostic population and poorly represented in clinical studies. We questioned if these patients are worth treating. In other words, if these patients received the most effective treatment, would it change the course of this disease? To our knowledge this is the first real-life study to evaluate this question in this low-survival population. (2) Methods: To tackle this question we performed a retrospective, multi-centric, real-life study, that reviewed relapsed HGSOC patients with ascites and/or pleural effusion...
December 28, 2023: Cancers
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