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JOURNAL ARTICLE
Aida Jlassi, Rim Rejaibi, Maroua Manai, Ghada Sahraoui, Fatma Zahra Guerfali, Lamia Charfi, Amel Mezlini, Mohamed Manai, Karima Mrad, Raoudha Doghri
INTRODUCTION: Immunotherapy by blocking immune checkpoints programmed death/ligand (PD1/PDL1) and cytotoxic T-lymphocyte-associated protein 4(CTLA4) has emerged as new therapeutic targets in cancer. However, their efficacy has been limited due to resistance. A new- checkpoint V-domain Ig-containing suppressor of T cell activation (VISTA) has appeared, but the use of its inhibition effect in combination with antibodies targeting PDL1/PD1and CTLA4 has not been reported in ovarian cancer...
2024: Frontiers in Oncology
#2
JOURNAL ARTICLE
Alexander M Xu, Marcela Haro, Ann E Walts, Ye Hu, Joshi John, Beth Y Karlan, Akil Merchant, Sandra Orsulic
High-grade serous ovarian carcinoma (HGSOC), the deadliest form of ovarian cancer, is typically diagnosed after it has metastasized and often relapses after standard-of-care platinum-based chemotherapy, likely due to advanced tumor stage, heterogeneity, and immune evasion and tumor-promoting signaling from the tumor microenvironment. To understand how spatial heterogeneity contributes to HGSOC progression and early relapse, we profiled an HGSOC tissue microarray of patient-matched longitudinal samples from 42 patients...
April 19, 2024: Science Advances
#3
JOURNAL ARTICLE
Hein S Zelisse, Robin A Hwan, Marc J van de Vijver, Frederike Dijk, Constantijne H Mom, Gerrit K J Hooijer, Mignon D J M van Gent, Malou L H Snijders
High-grade serous ovarian carcinoma (HGSOC) can be categorized into four gene expression-based subtypes, with supposedly distinct prognoses and treatment responses. Murakami et al. translated these gene expression-based subtypes into the histopathological mesenchymal, immunoreactive, solid and proliferative, and papilloglandular subtypes, showing differences in survival outcomes. Miyagawa et al. refined these criteria to improve the interobserver concordance. The current retrospective study evaluated the interobserver variability and the prognostic differences between the histopathologic subtypes using the criteria of both Murakami et al...
April 16, 2024: Virchows Archiv: An International Journal of Pathology
#4
JOURNAL ARTICLE
Rui Hou, Yadong Wang, Shiyao Cao, Xinrui Sun, Luo Jiang
High-grade serous ovarian cancer (HGSOC) remains the most lethal female cancer by far. Herein, clinical HGSOC samples had higher N6 -methyladenosine (m6 A) modification than normal ovarian tissue, and its dysregulation had been reported to drive aberrant transcription and translation programs. However, Kringle containing transmembrane protein 2 (KREMEN2) and its m6 A modification have not been fully elucidated in HGSOC. In this study, the data from the high-throughput mRNA sequencing (RNA-seq) of clinical samples were processed using the weighted correlation network analysis (WGCNA) and functional enrichment analysis...
April 12, 2024: Laboratory Investigation; a Journal of Technical Methods and Pathology
#5
JOURNAL ARTICLE
Marienid Flores-Colón, Mariela Rivera-Serrano, Víctor G Reyes-Burgos, José G Rolón, Josué Pérez-Santiago, María J Marcos-Martínez, Fatima Valiyeva, Pablo E Vivas-Mejía
Metastasis and drug resistance are major contributors to cancer-related fatalities worldwide. In ovarian cancer (OC), a staggering 70% develop resistance to the front-line therapy, cisplatin. Despite proposed mechanisms, the molecular events driving cisplatin resistance remain unclear. Dysregulated microRNAs (miRNAs) play a role in OC initiation, progression, and chemoresistance, yet few studies have compared miRNA expression in OC samples and cell lines. This study aimed to identify key miRNAs involved in the cisplatin resistance of high-grade-serous-ovarian-cancer (HGSOC), the most common gynecological malignancy...
March 28, 2024: International Journal of Molecular Sciences
#6
JOURNAL ARTICLE
Deshui Kong, Yu Wu, Qiyu Liu, Cuiyu Huang, Tongxia Wang, Zongyao Huang, Yan Gao, Yuan Li, Hongyan Guo
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the most aggressive and prevalent subtype of ovarian cancer and accounts for a significant portion of ovarian cancer-related deaths worldwide. Despite advancements in cancer treatment, the overall survival rate for HGSOC patients remains low, thus highlighting the urgent need for a deeper understanding of the molecular mechanisms driving tumorigenesis and for identifying potential therapeutic targets. Whole-exome sequencing (WES) has emerged as a powerful tool for identifying somatic mutations and alterations across the entire exome, thus providing valuable insights into the genetic drivers and molecular pathways underlying cancer development and progression...
April 12, 2024: European Journal of Medical Research
#7
REVIEW
Qurui Wang, Qinyuan Huang, Xiaowei Ying, Jinze Shen, Shiwei Duan
tRNA-derived small RNAs (tsRNAs) are novel small non-coding RNAs originating from mature or precursor tRNAs (pre-tRNA), typically spanning 14 to 30 nt. The Mitogen-activated protein kinases (MAPK) pathway orchestrates cellular responses, influencing proliferation, differentiation, apoptosis, and transformation. tsRNAs influence the expression of the MAPK signaling pathway by targeting specific proteins within the pathway. Presently, four MAPK-linked tsRNAs have implications in gastric cancer (GC) and high-grade serous ovarian cancer (HGSOC)...
2024: Frontiers in Genetics
#8
JOURNAL ARTICLE
Wenwen Lai, Ruixiang Xie, Chen Chen, Weiming Lou, Haiyan Yang, Libin Deng, Quqin Lu, Xiaoli Tang
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is the most prevalent and aggressive histological subtype of epithelial ovarian cancer. Around 80% of individuals will experience a recurrence within five years because of resistance to chemotherapy, despite initially responding well to platinum-based treatment. Biomarkers associated with chemoresistance are desperately needed in clinical practice. METHODS: We jointly analyzed the transcriptomic profiles of single-cell and bulk datasets of HGSOC to identify cell types associated with chemoresistance...
April 15, 2024: Heliyon
#9
JOURNAL ARTICLE
Elena Denisenko, Leanne de Kock, Adeline Tan, Aaron B Beasley, Maria Beilin, Matthew E Jones, Rui Hou, Dáithí Ó Muirí, Sanela Bilic, G Raj K A Mohan, Stuart Salfinger, Simon Fox, Khaing P W Hmon, Yen Yeow, Youngmi Kim, Rhea John, Tami S Gilderman, Emily Killingbeck, Elin S Gray, Paul A Cohen, Yu Yu, Alistair R R Forrest
High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections...
April 3, 2024: Nature Communications
#10
JOURNAL ARTICLE
Miguel Quiralte, Arantzazu Barquín, Mónica Yagüe Fernández, Paloma Navarro, Tatiana P Grazioso, Elena Sevillano, Juan F Rodriguez Moreno, Alejandra Balarezo-Saldivar, Héctor Peinado, Elena Izquierdo, Carlos Millán, Irene López Carrasco, Mario Prieto, Rodrigo Madurga de Lacalle, Ismael Fernández-Miranda, Sergio Ruiz-Llorente, Jesús García-Donas
Cancer-derived small extracellular vesicles (sEVs) are capable of modifying tumor microenvironment and promoting tumor progression. Ovarian cancer (OvCa) is a lethal malignancy that preferentially spreads through the abdominal cavity. Thus, the secretion of such vesicles into the peritoneal fluid could be a determinant factor in the dissemination and behavior of this disease. We designed a prospective observational study to assess the impact of peritoneal fluid-derived sEVs (PFD-sEVs) in OvCa clinical outcome...
April 2, 2024: Journal of Clinical Investigation
#11
JOURNAL ARTICLE
Elena Giudice, Tzu-Ting Huang, Jayakumar R Nair, Grant Zurcher, Ann McCoy, Darryl Nousome, Marc R Radke, Elizabeth M Swisher, Stanley Lipkowitz, Kristen Ibanez, Duncan Donohue, Tyler Malys, Min-Jung Lee, Bernadette Redd, Elliot Levy, Shraddha Rastogi, Nahoko Sato, Jane B Trepel, Jung-Min Lee
The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6)...
March 30, 2024: Nature Communications
#12
JOURNAL ARTICLE
Nisreen Al-Moghrabi, Maram Al-Showimi, Amal Alqahtani, Osama Almalik, Hamed Alhusaini, Ghdah Almalki, Ajawhara Saad, Elaf Alsunayi
Breast cancer (BC) and ovarian cancer (OC) are rapidly increasing in Saudi Arabia. BRCA1 and MGMT epimutations have been linked to a higher risk of these malignancies. The present research investigated the impact of these epimutations on the prevalence of BC and OC among Saudi women. DNA methylation was evaluated using methylation-specific PCR, whereas mRNA expression levels were assessed using qRT-PCR. We evaluated white blood cell (WBC)- BRCA1 methylation in 1958 Saudi women (908 BC patients, 223 OC patients, and 827 controls)...
March 7, 2024: International Journal of Molecular Sciences
#13
JOURNAL ARTICLE
Amy Jamieson, Juliana Sobral de Barros, Dawn R Cochrane, J Maxwell Douglas, Sameer Shankar, Branden J Lynch, Samuel Leung, Spencer Martin, Janine Senz, Amy Lum, Yvette Drew, C Blake Gilks, David G Huntsman, Jessica N McAlpine
PURPOSE: Shallow whole genome sequencing (sWGS) can detect copy number (CN) aberrations. In high-grade serous ovarian (HGSOC) sWGS identified CN signatures such as homologous recombination deficiency (HRD) to direct therapy. We applied sWGS with targeted sequencing to p53abn endometrial cancers (ECs) to identify additional prognostic stratification and therapeutic opportunities. EXPERIMENTAL DESIGN: sWGS and targeted panel sequencing was performed on formalin-fixed paraffin-embedded p53abn ECs...
March 27, 2024: Clinical Cancer Research
#14
JOURNAL ARTICLE
Lenka Kasikova, Jana Rakova, Michal Hensler, Tereza Lanickova, Jana Tomankova, Josef Pasulka, Jana Drozenova, Katerina Mojzisova, Anna Fialova, Sarka Vosahlikova, Jan Laco, Ales Ryska, Pavel Dundr, Roman Kocian, Tomas Brtnicky, Petr Skapa, Linda Capkova, Marek Kovar, Jan Prochazka, Ivan Praznovec, Vladimir Koblizek, Alice Taskova, Hisashi Tanaka, Robert Lischke, Fernando Casas Mendez, Jiri Vachtenheim, Viola Heinzelmann-Schwarz, Francis Jacob, Iain A McNeish, Michal J Halaska, Lukas Rob, David Cibula, Sandra Orsulic, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF ) cells and TIM3+ PD1+ , hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells...
March 21, 2024: Nature Communications
#15
JOURNAL ARTICLE
Nicole Pfarr, Karin von Schwarzenberg, Dario Zocholl, Sabine Merkelbach-Bruse, Janna Siemanowski, Eva-Maria Mayr, Sylvia Herold, Karsten Kleo, Lukas C Heukamp, Eva-Maria Willing, Michael Menzel, Ulrich Lehmann, Stephan Bartels, Shounak Chakraborty, Gustavo Baretton, Melanie C Demes, Claudia Döring, Daniel Kazdal, Jan Budczies, Roland Rad, Peter Wild, Yann Christinat, Thomas McKee, Peter Schirmacher, David Horst, Reinhard Büttner, Albrecht Stenzinger, Jalid Sehouli, Claudia Vollbrecht, Michael Hummel, Elena I Braicu, Wilko Weichert
PURPOSE: Poly(ADP-ribose) polymerase inhibitors (PARPi) have shown promising clinical results in the treatment of ovarian cancer. Analysis of biomarker subgroups consistently revealed higher benefits for patients with homologous recombination deficiency (HRD). The test that is most often used for the detection of HRD in clinical studies is the Myriad myChoice assay. However, other assays can also be used to assess biomarkers, which are indicative of HRD, genomic instability (GI), and BRCA1 / 2 mutation status...
March 2024: JCO Precision Oncology
#16
JOURNAL ARTICLE
Diana-Roxana Constantinescu, Andrei Sorop, Alina-Veronica Ghionescu, Daniela Lixandru, Vlad Herlea, Nicolae Bacalbasa, Simona Olimpia Dima
Introduction: High-grade serous ovarian carcinoma (HGSOC) remains a medical challenge despite considerable improvements in the treatment. Unfortunately, over 75% of patients have already metastasized at the time of diagnosis. Advances in understanding the mechanisms underlying how ascites cause chemoresistance are urgently needed to derive novel therapeutic strategies. This study aimed to identify the molecular markers involved in drug sensitivity and highlight the use of ascites as a potential model to investigate HGSOC treatment options...
2024: Frontiers in Pharmacology
#17
JOURNAL ARTICLE
Xiaoting Liu, Zhaojun Chen, Lahong Zhang
BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is a pathologic subtype of ovarian cancer (OC) with a more lethal prognosis. Extensive heterogeneity results in HGSOC being more susceptible to treatment resistance and adverse treatment effects. Revealing the heterogeneity involved is crucial. METHODS: We downloaded the single-cell RNA-seq (scRNA) data from GEO database and performed a scRNA analysis for cell landscape of HGSOC by using the Seurat package...
March 30, 2024: Heliyon
#18
Mengna Zhu, Si Sun, Lin Huang, Mengqing Chen, Jing Cai, Zehua Wang, Liqiong Cai
High-grade serous ovarian cancer (HGSOC) is the most common type of epithelial ovarian cancer with insidious onset, rapid growth, and invasive spread. Here, we reported the diagnosis and treatment of a 53-year-old patient with a history of hysterectomy aided by the 68 Ga-FAPI PET/MR scan. The patient was first presented to the local hospital with a lump on the left side of the neck with a biopsy suggesting metastatic cancer. Pelvic ultrasonography revealed two irregular masses. After admission, tumor markers, pathology consultation of the biopsy, and the 68 Ga-FAPI PET/MR scan were administered...
2024: American Journal of Nuclear Medicine and Molecular Imaging
#19
Daniel R Barnes, Jonathan P Tyrer, Joe Dennis, Goska Leslie, Manjeet K Bolla, Michael Lush, Amber M Aeilts, Kristiina Aittomäki, Nadine Andrieu, Irene L Andrulis, Hoda Anton-Culver, Adalgeir Arason, Banu K Arun, Judith Balmaña, Elisa V Bandera, Rosa B Barkardottir, Lieke P V Berger, Amy Berrington de Gonzalez, Pascaline Berthet, Katarzyna Białkowska, Line Bjørge, Amie M Blanco, Marinus J Blok, Kristie A Bobolis, Natalia V Bogdanova, James D Brenton, Henriett Butz, Saundra S Buys, Maria A Caligo, Ian Campbell, Carmen Castillo, Kathleen B M Claes, Sarah V Colonna, Linda S Cook, Mary B Daly, Agnieszka Dansonka-Mieszkowska, Miguel de la Hoya, Anna deFazio, Allison DePersia, Yuan Chun Ding, Susan M Domchek, Thilo Dörk, Zakaria Einbeigi, Christoph Engel, D Gareth Evans, Lenka Foretova, Renée T Fortner, Florentia Fostira, Maria Cristina Foti, Eitan Friedman, Megan N Frone, Patricia A Ganz, Aleksandra Gentry-Maharaj, Gord Glendon, Andrew K Godwin, Anna González-Neira, Mark H Greene, Jacek Gronwald, Aliana Guerrieri-Gonzaga, Ute Hamann, Thomas V O Hansen, Holly R Harris, Jan Hauke, Florian Heitz, Frans B L Hogervorst, Maartje J Hooning, John L Hopper, Chad D Huff, David G Huntsman, Evgeny N Imyanitov, Louise Izatt, Anna Jakubowska, Paul A James, Ramunas Janavicius, Esther M John, Siddhartha Kar, Beth Y Karlan, Catherine J Kennedy, Lambertus A L M Kiemeney, Irene Konstantopoulou, Jolanta Kupryjanczyk, Yael Laitman, Ofer Lavie, Kate Lawrenson, Jenny Lester, Fabienne Lesueur, Carlos Lopez-Pleguezuelos, Phuong L Mai, Siranoush Manoukian, Taymaa May, Iain A McNeish, Usha Menon, Roger L Milne, Francesmary Modugno, Jennifer M Mongiovi, Marco Montagna, Kirsten B Moysich, Susan L Neuhausen, Finn C Nielsen, Catherine Noguès, Edit Oláh, Olufunmilayo I Olopade, Ana Osorio, Laura Papi, Harsh Pathak, Celeste L Pearce, Inge S Pedersen, Ana Peixoto, Tanja Pejovic, Pei-Chen Peng, Beth N Peshkin, Paolo Peterlongo, C Bethan Powell, Darya Prokofyeva, Miquel Angel Pujana, Paolo Radice, Muhammad U Rashid, Gad Rennert, George Richenberg, Dale P Sandler, Naoko Sasamoto, Veronica W Setiawan, Priyanka Sharma, Weiva Sieh, Christian F Singer, Katie Snape, Anna P Sokolenko, Penny Soucy, Melissa C Southey, Dominique Stoppa-Lyonnet, Rebecca Sutphen, Christian Sutter, Manuel R Teixeira, Kathryn L Terry, Liv Cecilie V Thomsen, Marc Tischkowitz, Amanda E Toland, Toon Van Gorp, Ana Vega, Digna R Velez Edwards, Penelope M Webb, Jeffrey N Weitzel, Nicolas Wentzensen, Alice S Whittemore, Stacey J Winham, Anna H Wu, Siddhartha Yadav, Yao Yu, Argyrios Ziogas, Andrew Berchuck, Fergus J Couch, Ellen L Goode, Marc T Goodman, Alvaro N Monteiro, Kenneth Offit, Susan J Ramus, Harvey A Risch, Joellen M Schildkraut, Mads Thomassen, Jacques Simard, Douglas F Easton, Michelle R Jones, Georgia Chenevix-Trench, Simon A Gayther, Antonis C Antoniou, Paul D P Pharoah
BACKGROUND: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS). METHODS: We analyzed >22 million variants for 398,238 women. Associations were assessed separately by consortium and meta-analysed...
March 4, 2024: medRxiv
#20
JOURNAL ARTICLE
Vijayalalitha Ramanarayanan, Philipp Oberdoerffer
High-grade serous ovarian carcinoma (HGSOC) is the deadliest subtype of ovarian cancer. While PARP inhibitors (PARPi) have transformed the care of advanced HGSOC, PARPi resistance poses a major limitation to their clinical utility. DNA damage checkpoint signaling via ATR kinase can counteract PARPi-induced replication stress, making ATR an attractive therapeutic target in PARPi-resistant tumors. However, ATR inhibitor (ATRi) efficacy in the clinic is low, emphasizing the need for suitable combination treatments...
March 15, 2024: Cancer Research
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