keyword
https://read.qxmd.com/read/38341130/systematic-analysis-of-homologous-recombination-deficiency-testing-in-ovarian-cancer-development-of-recommendations-for-optimal-assay-performance
#1
JOURNAL ARTICLE
Marcel Romey, Fiona Rodepeter, Akira Hattesohl, Kristin Kaiser, Julia Teply-Szymanski, Florian Heitz, Annette Staebler, Violeta Serra, Albert Grass, Frederik Marmé, Kirsten M Timms, Philipp Harter, Alba Llop-Guevara, Stefan Kommoss, Jelena Boekhoff, Carsten Denkert
Homologous recombination deficiency (HRD) assays are an important element of personalized oncology in ovarian carcinomas, but the optimal tissue requirements for these complex molecular assays remain unclear. As a result, a considerable percentage of assays are not successful, leading to suboptimal diagnoses for these patients. In this study, we have systematically analyzed tumor and tissue parameters for HRD analysis in a large cohort of real-world cancer samples. The aim of this study is to give recommendations for pathologists and gynecologic oncologists for selection of tissue samples to maximize the success rate of HRD analyses...
February 8, 2024: Modern Pathology
https://read.qxmd.com/read/38290412/concordance-between-an-fda-approved-companion-diagnostic-and-an-alternative-assay-kit-for-assessing-homologous-recombination-deficiency-in-ovarian-cancer
#2
JOURNAL ARTICLE
Amy K Wehn, Ping Qiu, Jared Lunceford, Alexander Yarunin, Razvan Cristescu, Li Liu, Kyria Roessler, Sven Bilke, John R Day, Kirsten M Timms, Wilko Weichert, Matthew J Marton
OBJECTIVE: Authors evaluated the performance of a commercially available next-generation sequencing assay kit; this was based on genomic content from Illumina's TruSight™ Oncology 500 research assay that identifies BRCA variants and proprietary algorithms licensed from Myriad and, with additional genomic content, measures the homologous recombination deficiency (HRD) genomic instability score (GIS) in tumor tissue (TSO 500 HRD assay). METHODS: Data from the TSO 500 HRD assay were compared with data from the Myriad MyChoice®CDx PLUS assay (Myriad assay)...
January 29, 2024: Gynecologic Oncology
https://read.qxmd.com/read/37811043/gastric-lipoma-in-the-pyloric-antrum-a-rare-case-report
#3
Moatasem A Hussein Al-Janabi, Jollanar G Mohammad, Aya Y Mohsen, Zeina Alabbas, Omeed Rasheed, Samir Kannan, Ali K Daoud
INTRODUCTION AND IMPORTANCE: Gastric lipoma (GI) is a rare benign tumor of the stomach that arises from adipose tissue. It is often asymptomatic and is incidentally diagnosed on endoscopy or imaging studies. CASE PRESENTATION: A 66-year-old male presented with epigastric pain and acid reflux. Upper gastrointestinal endoscopy revealed a 3-cm submucosal lesion in the pyloric antrum. The patient underwent a subtotal gastrectomy. The specimen was sent to the pathology department...
October 2023: Annals of Medicine and Surgery
https://read.qxmd.com/read/37809048/rediscore-prospective-validation-of-a-pipeline-for-homologous-recombination-deficiency-analysis
#4
JOURNAL ARTICLE
Aikaterini Tsantikidi, Konstantinos Papazisis, Theofanis Floros, Maria Gazouli, Eirini Papadopoulou, Georgios Tsaousis, Georgios Nasioulas, Andra Mester, Kubelac Paul Milan, Bogdan Gozman, Vlad Afrasanie, Dana Lucia Stanculeanu, Oana Trifanescu, Florentina Pescaru, Claudia Militaru, Christos Papadimitriou
Tumors harboring homologous recombination deficiency (HRD) are considered optimal candidates for poly(ADP-ribose) polymerase 1 (PARP) inhibitor treatment. Such deficiency can be detected by analyzing breast cancer type ( BRCA)1/2 gene mutations, as well as mutations in other genes of the homologous recombination pathway. The algorithmic measurement of the HRD effect by identifying genomic instability (GI) has been used as biomarker. As compared with the direct measurement of somatic gene alterations, this approach increases the number of patients who could benefit from PARP inhibitor treatment...
November 2023: Oncology Letters
https://read.qxmd.com/read/37593108/novel-albumin-binding-multifunctional-probe-for-synergistic-enhancement-of-fl-mr-dual-modal-imaging-and-photothermal-therapy
#5
JOURNAL ARTICLE
Cheng Yu, Zhuyuan Ding, Huan Liu, Yulu Ren, Minping Zhang, Qiuling Liao, Tao Luo, Lujing Gao, Shiyi Lyu, Huiwen Tan, Linan Hu, Zhu Chen, Pengfei Xu, Enhua Xiao
The fluorescence/magnetic resonance (FL/MR) dual-modal imaging could provide accurate tumor visualization to guide photothermal therapy (PTT) of cancer, which has attracted widespread attention from scientists. However, facile and effective strategies to synergistically enhance fluorescence intensity, MR contrast and photothermal efficacy have rarely been reported. This study presents a novel multifunctional probe Gd-EB-ICG (GI) for FL/MR dual-modal imaging-guided PTT of cancer. GIs can self-assemble with endogenous albumin to form drug-albumin complexes (GIAs), which exhibit excellent biocompatibility...
2023: Frontiers in Chemistry
https://read.qxmd.com/read/37589839/identifying-homologous-recombination-deficiency-in-breast-cancer-genomic-instability-score-distributions-differ-among-breast-cancer-subtypes
#6
JOURNAL ARTICLE
Lauren Lenz, Chris Neff, Cara Solimeno, Elizabeth S Cogan, Vandana G Abramson, Judy C Boughey, Carla Falkson, Matthew P Goetz, James M Ford, William J Gradishar, Rachel C Jankowitz, Virginia G Kaklamani, P Kelly Marcom, Andrea L Richardson, Anna Maria Storniolo, Nadine M Tung, Shaveta Vinayak, Darren R Hodgson, Zhongwu Lai, Simon Dearden, Bryan T Hennessy, Erica L Mayer, Gordon B Mills, Thomas P Slavin, Alexander Gutin, Roisin M Connolly, Melinda L Telli, Vered Stearns, Jerry S Lanchbury, Kirsten M Timms
PURPOSE: A 3-biomarker homologous recombination deficiency (HRD) score is a key component of a currently FDA-approved companion diagnostic assay to identify HRD in patients with ovarian cancer using a threshold score of ≥ 42, though recent studies have explored the utility of a lower threshold (GIS ≥ 33). The present study evaluated whether the ovarian cancer thresholds may also be appropriate for major breast cancer subtypes by comparing the genomic instability score (GIS) distributions of BRCA1/2-deficient estrogen receptor-positive breast cancer (ER + BC) and triple-negative breast cancer (TNBC) to the GIS distribution of BRCA1/2-deficient ovarian cancer...
August 17, 2023: Breast Cancer Research and Treatment
https://read.qxmd.com/read/37444554/development-of-the-noggo-gis-v1-assay-a-comprehensive-hybrid-capture-based-ngs-assay-for-therapeutic-stratification-of-homologous-repair-deficiency-driven-tumors-and-clinical-validation
#7
JOURNAL ARTICLE
Eva-Maria Willing, Claudia Vollbrecht, Christine Vössing, Peggy Weist, Simon Schallenberg, Johanna M Herbst, Stefanie Schatz, Balázs Jóri, Guillaume Bataillon, Philipp Harter, Vanda Salutari, Antonio Gonzáles Martin, Ignace Vergote, Nicoletta Colombo, Julia Roeper, Tobias Berg, Regina Berger, Bettina Kah, Trine Jakobi Noettrup, Markus Falk, Kathrin Arndt, Andreas Polten, Isabelle Ray-Coquard, Franziska Selzam, Judith Pirngruber, Stefanie Schmidt, Michael Hummel, Markus Tiemann, David Horst, Jalid Sehouli, Eric Pujade-Lauraine, Katharina Tiemann, Elena Ioana Braicu, Lukas C Heukamp
The worldwide approval of the combination maintenance therapy of olaparib and bevacizumab in advanced high-grade serous ovarian cancer requires complex molecular diagnostic assays that are sufficiently robust for the routine detection of driver mutations in homologous recombination repair (HRR) genes and genomic instability (GI), employing formalin-fixed (FFPE) paraffin-embedded tumor samples without matched normal tissue. We therefore established a DNA-based hybrid capture NGS assay and an associated bioinformatic pipeline that fulfils our institution's specific needs...
June 30, 2023: Cancers
https://read.qxmd.com/read/37392382/integration-of-cancer-related-genetic-landscape-of-eph-receptors-and-ephrins-with-proteomics-identifies-a-crosstalk-between-ephb6-and-egfr
#8
JOURNAL ARTICLE
Glinton Hanover, Frederick S Vizeacoumar, Sara L Banerjee, Raveena Nair, Renuka Dahiya, Ana I Osornio-Hernandez, Alain Morejon Morales, Tanya Freywald, Juha P Himanen, Behzad M Toosi, Nicolas Bisson, Franco J Vizeacoumar, Andrew Freywald
Eph receptors and their ephrin ligands are viewed as promising targets for cancer treatment; however, targeting them is hindered by their context-dependent functionalities. To circumvent this, we explore molecular landscapes underlying their pro- and anti-malignant activities. Using unbiased bioinformatics approaches, we construct a cancer-related network of genetic interactions (GIs) of all Ephs and ephrins to assist in their therapeutic manipulation. We also apply genetic screening and BioID proteomics and integrate them with machine learning approaches to select the most relevant GIs of one Eph receptor, EPHB6...
June 30, 2023: Cell Reports
https://read.qxmd.com/read/37082521/recurrence-rate-in-early-stage-epithelial-ovarian-cancer-is-there-a-role-for-upfront-maintenance-with-parp-inhibitors-in-stages-i-and-ii
#9
JOURNAL ARTICLE
Monica D Levine, David M O'Malley, Paulina J Haight, Leigha Senter, Vincent Wagner, Kristin L Bixel, David E Cohn, Larry J Copeland, Casey M Cosgrove, Eric M McLaughlin, Floor J Backes
OBJECTIVE: To determine the recurrence rate and survival among early-stage epithelial ovarian cancer cases considering homologous recombination deficiency (HRD) status. METHODS: Single institution retrospective study of stage I/II EOC patients from 2017 to 2020. HRD was defined as evidence of germline or somatic BRCA mutation, or loss of heterozygosity (LOH)/genomic instability (GIS) as determined by companion diagnostic tests. Kaplan-Meier analyses were performed...
April 2023: Gynecologic Oncology Reports
https://read.qxmd.com/read/37072323/homologous-recombination-deficiency-in-newly-diagnosed-figo-stage-iii-iv-high-grade-epithelial-ovarian-cancer-a-multi-national-observational-study
#10
JOURNAL ARTICLE
Robert D Morgan, Andrew R Clamp, Bethany M Barnes, Kirsten Timms, Helene Schlecht, Laura Yarram-Smith, Yvonne Wallis, Mikel Valganon-Petrizan, Suzanne MacMahon, Rhian White, Sian Morgan, Sarah McKenna, Emma Hudson, Laura Tookman, Angela George, Ranjit Manchanda, Sudha S Sundar, Shibani Nicum, James D Brenton, Rebecca S Kristeleit, Susana Banerjee, Iain A McNeish, Jonathan A Ledermann, Stephen S Taylor, D Gareth R Evans, Gordon C Jayson
OBJECTIVE: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. METHODS: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer...
April 18, 2023: International Journal of Gynecological Cancer
https://read.qxmd.com/read/37067532/clinical-relevance-of-brca1-promoter-methylation-testing-in-ovarian-cancer-patients
#11
JOURNAL ARTICLE
Félix Blanc-Durand, Roseline Tang, Margaux Pommier, Marzieh Nashvi, Sophie Cotteret, Catherine Genestie, Audrey Le Formal, Patricia Pautier, Judith Michels, Maria Kfoury, Robert Hervé, Sylvie Mengue, Estelle Wafo, Antoine Elies, Gregoire Miailhe, Jennifer Uzan, Etienne Rouleau, Alexandra Leary
PURPOSE: Homologous-recombination deficiency (HRD) is closely related to PARPi benefit in ovarian cancer (OC). The capacity of BRCA1 promoter methylation to predict prognosis and HRD status remains unclear. We aimed to correlate BRCA1 promoter methylation levels in patients with high-grade OC to HRD status and clinical behavior to assess its clinical relevance. DESIGN: This is a retrospective monocentric analysis of patients centrally tested for genomic-instability score (GIS) by MyChoice CDx (Myriad Genetics)...
April 17, 2023: Clinical Cancer Research
https://read.qxmd.com/read/37013791/ghost-ileostomy-versus-loop-ileostomy-following-oncologic-resection-for-rectal-cancer-a-systematic-review-and-meta-analysis
#12
REVIEW
Tyler McKechnie, Jay Lee, Yung Lee, Léa Tessier, Nalin Amin, Aristithes Doumouras, Dennis Hong, Cagla Eskicioglu
OBJECTIVE: The aim of this study was to compare ghost ileostomy (GI) and loop ileostomy (LI) in patients undergoing oncologic resection for rectal cancer in terms of postoperative morbidity. SUMMARY BACKGROUND DATA: LIs are often fashioned to protect downstream anastomoses following oncologic resection for low rectal cancer at medium-to-high risk of anastomotic leak. More recently, GIs have been utilized in patients with low-to-medium risk anastomoses to reduce the rate of unnecessary stomas...
August 2023: Surgical Innovation
https://read.qxmd.com/read/36970052/-ad-hoc-analysis-of-the-phase-iii-engot-ov16-nova-study-niraparib-efficacy-in-germline-brca-wild-type-recurrent-ovarian-cancer-with-homologous-recombination-repair-defects
#13
JOURNAL ARTICLE
Mansoor Raza Mirza, Gabriel Lindahl, Sven Mahner, Andrés Redondo, Michel Fabbro, Bobbie J Rimel, Jørn Herrstedt, Amit M Oza, Ulrich Canzler, Jonathan S Berek, Antonio González-Martín, Phillipe Follana, Rosemary Lord, Masoud Azodi, Kasey Estenson, Zebin Wang, Yong Li, Divya Gupta, Ursula Matulonis, Bin Feng
UNLABELLED: In this analysis, we examined the relationship between progression-free survival (PFS) and mutation status of 18 homologous recombination repair (HRR) genes in patients in the non-germline BRCA -mutated (non-g BRCA m) cohort of the ENGOT-OV16/NOVA trial (NCT01847274), which evaluated niraparib maintenance therapy for patients with recurrent ovarian cancer. This post hoc exploratory biomarker analysis was performed using tumor samples collected from 331 patients enrolled in the phase III ENGOT-OV16/NOVA trial's non-g BRCA m cohort...
November 2022: Cancer Res Commun
https://read.qxmd.com/read/36840413/an-integrative-epigenomic-approach-identifies-elf3-as-an-oncogenic-regulator-in-ascl1-positive-neuroendocrine-carcinoma
#14
JOURNAL ARTICLE
Masafumi Horie, Hidenori Tanaka, Masami Suzuki, Yoshihiko Sato, So Takata, Erina Takai, Naoya Miyashita, Akira Saito, Yoichiro Nakatani, Shinichi Yachida
Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC...
February 24, 2023: Cancer Science
https://read.qxmd.com/read/36818502/the-importance-of-inflammatory-markers-in-detection-of-complications-in-patients-with-gastric-cancer-undergoing-the-enhanced-recovery-after-surgery-eras-protocol-a-prospective-cohort-study
#15
JOURNAL ARTICLE
Alpen Yahya Gumusoglu, Hamit Ahmet Kabuli, Murat Cikot, Nilgun Isıksacan, Pinar Kasapoglu, Ertug Can Cayırcı, Sinan Binboga, Mehmet Karabulut, Halil Alıs
INTRODUCTION: Early diagnosis reduces mortality and morbidity rates in gastrointestinal system (GIS) anastomoses. AIM: The aim of the present study was to investigate the importance of some substances that were used to detect major complications early in patients who were treated in line with the Enhanced Recovery After Surgery (ERAS) protocol for gastric cancer. Factors included in the study were interleukin-1 β (IL-1 β ), tumor necrosis factor- α (TNF- α ), C-reactive protein (CRP), procalcitonin (PCT) and white blood cell (WBC)...
December 2022: Videosurgery and Other Miniinvasive Techniques
https://read.qxmd.com/read/36765776/implementing-hrd-testing-in-routine-clinical-practice-on-patients-with-primary-high-grade-advanced-ovarian-cancer
#16
JOURNAL ARTICLE
Florian Heitz, Beyhan Ataseven, Claudia Staniczok, Carsten Denkert, Kerstin Rhiem, Eric Hahnen, Sebastian Heikaus, Malak Moubarak, Julia Welz, Timoleon Dagres, Vasilios Vrentas, Mareike Bommert, Stephanie Schneider, Nicole Concin, Philipp Harter
The chemotherapy backbone for patients with high-grade advanced epithelial ovarian cancer (HG-AOC) is carboplatin and paclitaxel followed by a maintenance therapy either with bevacizumab, with a PARP inhibitor, or with a combination of both, which is defined by the presence of a homologous recombination deficiency (HRD) and by the BRCA1/2 status. This study included patients with a primary diagnosis of HG-AOC treated between December 2019 and December 2021. The HRD status was measured using the Myriad myChoice® test on all the patients with an indication for tumor HRD testing...
January 29, 2023: Cancers
https://read.qxmd.com/read/36716415/homologous-recombination-repair-gene-mutations-to-predict-olaparib-plus-bevacizumab-efficacy-in-the-first-line-ovarian-cancer-paola-1-engot-ov25-trial
#17
RANDOMIZED CONTROLLED TRIAL
Eric Pujade-Lauraine, Jessica Brown, Alan Barnicle, Jonathan Wessen, Pierre Lao-Sirieix, Steven W Criscione, Andreas du Bois, Domenica Lorusso, Ignacio Romero, Edgar Petru, Hiroyuki Yoshida, Ignace Vergote, Nicoletta Colombo, Sakari Hietanen, Magali Provansal, Barbara Schmalfeldt, Sandro Pignata, Cristina Martín Lorente, Dominique Berton, Ingo B Runnebaum, Isabelle Ray-Coquard
PURPOSE: The PAOLA-1/ENGOT-ov25 trial of maintenance olaparib plus bevacizumab for newly diagnosed advanced high-grade ovarian cancer demonstrated a significant progression-free survival (PFS) benefit over placebo plus bevacizumab, particularly in patients with homologous recombination deficiency (HRD)-positive tumors. We explored whether mutations in non- BRCA1 or BRCA2 homologous recombination repair (non-BRCA HRRm) genes predicted benefit from olaparib plus bevacizumab in PAOLA-1. METHODS: Eight hundred and six patients were randomly assigned (2:1)...
January 2023: JCO Precision Oncology
https://read.qxmd.com/read/36672477/association-of-genomic-instability-score-tumor-mutational-burden-and-tumor-infiltrating-lymphocytes-as-biomarkers-in-uterine-serous-carcinoma
#18
JOURNAL ARTICLE
Elizabeth A Bloom, Pamela N Peters, Regina Whitaker, Shonagh Russell, Benjamin Albright, Shelly Cummings, Kirsten M Timms, Thomas Slavin, Braden Probst, Kyle C Strickland, Rebecca A Previs
BACKGROUND: Uterine serous carcinomas represent 10% of uterine carcinomas but account for nearly 40% of deaths from the disease. Improved molecular characterization of these tumors is instrumental in guiding targeted treatment and improving outcomes. This study assessed the genomic instability score (GIS), tumor mutational burden (TMB), and tumor-infiltrating lymphocytes (TILs) in patients with USC. METHODS: A retrospective cohort study evaluated patients with USC following staging surgery...
January 15, 2023: Cancers
https://read.qxmd.com/read/36383269/clinical-efficacy-of-tandospirone-on-functional-dyspepsia-patients-with-anxiety-a-randomized-placebo-controlled-study
#19
JOURNAL ARTICLE
Lulu Liu, Wenguang Yang, Ya Lu, Jue Wang, Yan Zheng, Sai Gu
BACKGROUND: Functional dyspepsia (FD) is characterized with multiple symptoms of indigestion and often accompanied with anxiety. However, there is currently an absence of effective treatment. Tandospirone is commonly used to treat generalized anxiety disorders. Whether tandospirone can improve the clinical symptoms of FD remain unknown. AIMS: The present study was designed to explore the pharmacological effect of tandospirone on FD patient with anxiety, and the potential mechanisms were also elucidated...
November 16, 2022: Digestive Diseases and Sciences
https://read.qxmd.com/read/36246596/development-and-validation-of-a-combined-glycolysis-and-immune-prognostic-signature-for-lung-squamous-cell-carcinoma
#20
JOURNAL ARTICLE
Qiang Huang, Shan Yang, Hao Yan, Hong Chen, Yuzhu Wang, Yang Wang
Background: The involvement of glycolysis in the regulation of the tumor immune microenvironment has become a novel research field. In this study, the specific functions and clinical significance of glycolysis-related genes (GRGs) and immune-related genes (IRGs) were systematically characterized in lung squamous cell carcinoma (LUSC). Methods: We evaluated the prognostic value, interactions, somatic mutations, and copy-number variations of GRGs and IRGs in LUSC from a dataset of The Cancer Genome Atlas (TCGA)...
2022: Frontiers in Genetics
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