Article
Oncology
Xian Chen, Dong Yang, Jason P. W. Carey, Cansu Karakas, Constance Albarracin, Aysegul A. Sahin, Banu K. Arun, Merih Guray Durak, Mi Li, Mehrnoosh Kohansal, Tuyen N. Bui, Min-Jin Ha, Kelly K. Hunt, Khandan Keyomarsi
Summary: Triple-negative breast cancer (TNBC) is a subtype of invasive breast cancer with poor survival outcomes. High levels of cyclin E in tumors are associated with BRCA1/2 alterations and worse clinical prognosis. Combination therapy with PARP and Wee1 kinase inhibitors in TNBC cells with cyclin E overexpression or BRCA1 mutations results in synergistic cell death through induction of replicative stress and downregulation of DNA repair. Identifying patients with high replicative stress properties through biomarkers like cyclin E or BRCA mutations may lead to more effective treatment with combination therapy.
Article
Automation & Control Systems
Guanxing Chen, Haohuai He, Lu Zhao, Kuen-Bao Chen, Siyuan Li, Calvin Yu-Chian Chen
Summary: Recent research has identified CDK7, CDK9, and CCNT1 as players in transcriptional misregulation in cancer. Using a combination of traditional virtual screening and artificial intelligence models, we identified potential multi-target inhibitors from the FDA database. Our results showed that Adaptive Boosting-Decision Tree Regression (AdaBoost), Support Vector Machine Regression (SVR), and Ridge Regression (Ridge) achieved good results in predicting CDK7 inhibitors, while AdaBoost, Random Forest (RF), and Ridge performed well for CDK9 inhibitors. Based on molecular dynamics simulations and analysis, we propose two potential multi-target inhibitors for TNBC.
CHEMOMETRICS AND INTELLIGENT LABORATORY SYSTEMS
(2022)
Article
Biochemistry & Molecular Biology
Che-Pei Kung, Kyle A. Cottrell, Sua Ryu, Emily R. Bramel, Raleigh D. Kladney, Emily A. Bao, Eric C. Freeman, Thwisha Sabloak, Leonard Maggi Jr., Jason D. Weber
Summary: Triple-negative breast cancer (TNBC) is the deadliest form of breast cancer with no targeted therapy available. The ADAR1 enzyme, highly expressed in TNBC, is essential for the survival of TNBC cell lines. Knockdown of ADAR1 in TNBC cells attenuates proliferation and tumorigenesis, leading to translational repression and elevated IFN stimulated gene expression. These findings establish ADAR1 as a novel therapeutic target for TNBC tumors.
Article
Multidisciplinary Sciences
Xu Yang, Li Deng, Xianhong Diao, Siyuan Yang, Li Zou, Qin Yang, Jian Li, Jianyun Nie, Lina Zhao, Baowei Jiao
Summary: The compound zinc pyrithione (ZnPT) has been identified as a potent inhibitor of triple-negative breast cancer (TNBC) progression by disrupting copper homeostasis, offering a potential experimental foundation for exploring cuproptosis as a target for drug discovery in TNBC patients.
Article
Multidisciplinary Sciences
Xiao Qian Wang, Esther Danenberg, Chiun-Sheng Huang, Daniel Egle, Maurizio Callari, Begona Bermejo, Matteo Dugo, Claudio Zamagni, Marc Thill, Anton Anton, Stefania Zambelli, Stefania Russo, Eva Maria Ciruelos, Richard Greil, Balazs Gyorffy, Vladimir Semiglazov, Marco Colleoni, Catherine M. Kelly, Gabriella Mariani, Lucia Del Mastro, Olivia Biasi, Robert S. Seitz, Pinuccia Valagussa, Giuseppe Viale, Luca Gianni, Giampaolo Bianchini, H. Raza Ali
Summary: Imaging mass cytometry reveals that the multicellular dynamics in triple-negative breast cancer treated with immune checkpoint blockade (ICB) play a crucial role in determining treatment response. Key factors such as cell phenotype, activation state, and spatial location influence the effectiveness of ICB. By understanding the impact of multicellular organization, we can better guide adaptive therapy and achieve precision immuno-oncology.
Article
Cell Biology
Hai Wang, Xingyu Rong, Gan Zhao, Yifan Zhou, Yi Xiao, Ding Ma, Xi Jin, Yonglin Wu, Yuchen Yan, Hao Yang, Yuan Zhou, Manning Qian, Chen Niu, Xin Hu, Da-Qiang Li, Qingyun Liu, Yumei Wen, Yi-Zhou Jiang, Chao Zhao, Zhi-Ming Shao
Summary: The metabolite TMAO in the microbiota of breast cancer patients enhances the response to immunotherapy by promoting an activated immune microenvironment.
Article
Multidisciplinary Sciences
Saber Yari Bostanabad, Senem Noyan, Bala Gur Dedeoglu, Hakan Gurdal
Summary: Beta-arrestins play a significant role in cancer cell function, particularly in breast cancer cells. Modulating their expression levels can influence cell proliferation, invasion, cell cycle genes, and anticancer signaling pathways.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Jodi M. Carter, Saranya Chumsri, Douglas A. Hinerfeld, Yaohua Ma, Xue Wang, David Zahrieh, David W. Hillman, Kathleen S. Tenner, Jennifer M. Kachergus, Heather Ann Brauer, Sarah E. Warren, David Henderson, Ji Shi, Yi Liu, Heikki Joensuu, Henrik Lindman, Roberto A. Leon-Ferre, Judy C. Boughey, Minetta C. Liu, James N. Ingle, Krishna R. Kalari, Fergus J. Couch, Keith L. Knutson, Matthew P. Goetz, Edith A. Perez, E. Aubrey Thompson
Summary: The use of spatial immunobiomarker quantitation is being actively explored in the prognosis and prediction of therapy in triple-negative breast cancer (TNBC). In this study, high-plex quantitative digital spatial profiling was used to analyze the immune protein microenvironments in treatment-naive TNBC. The results show that immune protein profiles differ significantly in intraepithelial and adjacent stromal microenvironments, and the enrichment of certain immune proteins is associated with better outcomes, highlighting the importance of spatial microenvironments in predicting the prognosis of TNBC.
NATURE COMMUNICATIONS
(2023)
Review
Cell Biology
Rafaela Fagundes, Leonardo K. Teixeira
Summary: DNA replication must be precisely controlled, and cell cycle transitions are regulated by the Cyclin-Dependent Kinases (CDKs) family. The Cyclin E/CDK2 complex controls cell cycle progression and DNA replication through phosphorylation of specific substrates in normal cycles, while its oncogenic activation causes replication stress and genomic instability.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ebtihal H. Mustafa, Geraldine Laven-Law, Zoya Kikhtyak, Van Nguyen, Simak Ali, Alex A. Pace, Richard Iggo, Alemwork Kebede, Ben Noll, Shudong Wang, Jean M. Winter, Amy R. Dwyer, Wayne D. Tilley, Theresa E. Hickey
Summary: Targeting transcription via CDK9 could be a potential therapeutic strategy for TNBC. Preclinical studies showed that a selective CDK9 inhibitor, CDDD11-8, effectively inhibited proliferation, induced cell cycle arrest, and increased apoptosis of TNBC cells in vitro and in vivo, without apparent toxicity to normal tissues.
Article
Oncology
Anthony Cheung, Alicia M. Chenoweth, Jelmar Quist, Heng Sheng Sow, Christina Malaktou, Riccardo Ferro, Ricarda M. Hoffmann, Gabriel Osborn, Eirini Sachouli, Elise French, Rebecca Marlow, Katie E. Lacy, Sophie Papa, Anita Grigoriadis, Sophia N. Karagiannis
Summary: This study demonstrates that suboptimal dosing of the CDK2 inhibitor SNS-032 reduces the viability of TNBC cells and upregulates PD-L1 expression in surviving cancer cells. Additionally, SNS-032 treatment promotes the infiltration of human immune cells in TNBC tumors. Combination therapy of suboptimal SNS-032 and anti-PD-L1 antibody significantly restricts tumor growth. These findings suggest that suboptimal CDK inhibition may enhance the effectiveness of checkpoint immunotherapy in TNBC.
Article
Biochemistry & Molecular Biology
Isaac Jardin, Raquel Diez-Bello, Debora Falcon, Sandra Alvarado, Sergio Regodon, Gines M. Salido, Tarik Smani, Juan A. Rosado
Summary: Melatonin has been shown to effectively reduce tumor growth in TNBC cells, potentially through modulation of the SOCE pathway and TRPC6 expression. The inhibitory effects of melatonin on Ca2+ influx in TNBC cells suggest a novel antitumoral mechanism involving TRPC6 downregulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Lake-Ee Quek, Michelle van Geldermalsen, Yi Fang Guan, Kanu Wahi, Chelsea Mayoh, Seher Balaban, Angel Pang, Qian Wang, Mark J. Cowley, Kristin K. Brown, Nigel Turner, Andrew J. Hoy, Jeff Holst
Summary: This study reveals that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, which increases TCA cycle fluxes and replenishes TCA cycle intermediates. The coupling of glucose and glutamine catabolism hampers TNBC cells' ability to oxidize glucose when glutamine is limiting.
Article
Multidisciplinary Sciences
Courtney D. Dill, Eric B. Dammer, Ti'ara L. Griffen, Nicholas T. Seyfried, James W. Lillard
Summary: The study aimed to identify drivers of triple-negative breast cancer survival time by analyzing transcriptomic data and network communities, resulting in predictive signatures for TNBC prognosis. By integrating various analytical approaches, a panel of key survival genes with potential clinical utility was uncovered.
Article
Multidisciplinary Sciences
Pengjun Qiu, Qiaonan Guo, Qingzhi Yao, Jianpeng Chen, Jianqing Lin
Summary: This study identified 390 common DEGs, with 250 up-regulated and 140 down-regulated genes, in AR positive TNBC. 13 hub genes were selected, among which CCNB1 was found to be significantly associated with poor survival in TNBC patients. A potential miRNA-CCNB1 regulatory axis involving hsa-miR-3163 was also constructed as a promising prognostic marker and therapeutic target for AR positive TNBC.
Article
Oncology
Mieke C. Zwager, Rico Bense, Stijn Waaijer, Si-Qi Qiu, Hetty Timmer-Bosscha, Elisabeth G. E. de Vries, Carolien P. Schroder, Bert van der Vegt
Summary: The purpose of this study was to optimize the assessment of tumour-associated macrophage subsets in different breast cancer subtypes and relate them to clinicopathological characteristics and clinical outcomes. The results showed that CD68+, CD163+, and CSF-1R+ macrophages correlated with tumour grade in Luminal-B breast cancer. However, total or subset TAM numbers did not correlate with disease outcome in any breast cancer subtype.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Pathology
Ximena Baez-Navarro, Mieke R. van Bockstal, Dienna Nawawi, Glenn Broeckx, Cecile Colpaert, Shusma C. Doebar, Marieke C. H. Hogenes, Esther Koop, Kathleen Lambein, Dieter J. E. Peeters, Renata H. J. A. Sinke, Johannes Bastiaan van Brakel, Jose van der Starre-Gaal, Bert van der Vegt, Koen van de Vijver, Celien P. H. Vreuls, Willem Vreuls, Pieter J. Westenend, Carolien H. M. van Deurzen
Summary: A multicenter international study assessed the interobserver agreement in specific HER2 immunohistochemistry scores for breast cancer. The current guidelines may not be sufficient for identifying HER2-low tumors. Modifying the scoring criteria or adding fluorescent in situ hybridization may improve the agreement.
Article
Otorhinolaryngology
Karlijn van den Bovenkamp, Bert van der Vegt, Gyorgy B. Halmos, Lorian Slagter-Menkema, Johannes A. Langendijk, Boukje A. C. van Dijk, Ed Schuuring, Bernard F. A. M. van der Laan
Summary: This study examined the predictive value of various tumor markers in patients with advanced-stage laryngeal squamous cell carcinoma, and found that overexpression of HIF-1α was associated with locoregional recurrence.
EUROPEAN ARCHIVES OF OTO-RHINO-LARYNGOLOGY
(2023)
Article
Oncology
E. C. de Heer, C. E. Zois, E. Bridges, B. van der Vegt, H. Sheldon, W. A. Veldman, M. C. Zwager, T. van der Sluis, S. Haider, T. Morita, O. Baba, C. P. Schroder, S. de Jong, A. L. Harris, M. Jalving
Summary: The study found that the gene GYS1 is related to tumor growth and therapy resistance in breast cancer, especially in triple-negative breast cancer. Inhibiting GYS1 weakens the proliferation ability of breast cancer cells and makes them more sensitive to inhibition of mitochondrial proteostasis.
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
(2023)
Article
Medicine, General & Internal
Navin Suthahar, Dongyu Wang, Joseph Pierre Aboumsallem, Canxia Shi, Sanne de Wit, Elizabeth E. Liu, Emily S. Lau, Stephan J. L. Bakker, Ron. T. Gansevoort, Bert van der Vegt, Manol Jovani, Bernard E. Kreger, Greta Lee Splansky, Emelia J. Benjamin, Ramachandran S. Vasan, Martin G. Larson, Daniel Levy, Jennifer E. Ho, Rudolf A. de Boer
Summary: This study evaluated the value of serial CRP measurements in predicting the risk of CVD, cancer, and mortality. The results showed that both baseline CRP levels and subsequent increases in CRP were associated with future CVD, cancer, and mortality.
MAYO CLINIC PROCEEDINGS
(2023)
Article
Oncology
Andra S. Martinikova, Miroslav Stoyanov, Anna Oravetzova, Yannick P. Kok, Shibo Yu, Jana Dobrovolna, Pavel Janscak, Marcel van Vugt, Libor Macurek
Summary: Oncogene-induced replication stress is a major cause of genome instability in cancer cells. This study reveals that increased activity of PPM1D exacerbates replication stress caused by cyclin E1 overexpression, leading to abnormal cell cycle progression and accumulation of DNA copy number alterations. Pharmacological inhibition of PPM1D can alleviate replication stress-induced genome instability.
MOLECULAR ONCOLOGY
(2024)
Article
Rheumatology
Martha S. van Ginkel, Suzanne Arends, Bert van der Vegt, Marcel Nijland, Fred K. L. Spijkervet, Arjan Vissink, Frans G. M. Kroese, Andor W. J. M. Glaudemans, Hendrika Bootsma
Summary: This study aimed to assess the usefulness of [F-18]-fluorodeoxyglucose (FDG)-PET/CT in discriminating primary Sjögren's syndrome (pSS) patients with and without lymphomas, as well as evaluating systemic disease activity in pSS. The results showed that FDG-PET/CT can assist in identifying pSS-associated lymphomas and detecting systemic manifestations in pSS patients.
Article
Oncology
Annechien Stuursma, Bert van der Vegt, Liesbeth Jansen, Lieke P. V. Berger, Marian J. E. Mourits, Geertruida H. de Bock
Summary: This study investigated the effect of RRSO on breast cancer incidence and histopathological features in female BRCA1/2 GPV carriers. The results showed that RRSO did not decrease the risk of breast cancer in BRCA1 and BRCA2 GPV carriers, but the breast cancer cases diagnosed after RRSO tended to be smaller.
Article
Public, Environmental & Occupational Health
Kelly M. Castaneda, Grigory A. Sidorenkov, Jolien de Waard, Marcel J. W. Greuter, Bert Van der Vegt, Inge M. C. M. de Kok, Albert G. Siebers, Karin M. Vermeulen, G. Bea A. Wisman, Ed Schuuring, Geertruida H. de Bock
Summary: This study aimed to evaluate the true participation rate of cervical cancer screening (CCS) by extending the time window for defining participation and to analyze the impact of sociodemographic determinants on participation delays. The findings showed that a 36-month window better reflected the actual participation rate and that delayed participation was associated with younger age, higher education, the high-risk human papillomavirus test-based program, and pregnancy. This suggests the importance of considering these factors when designing and promoting CCS programs.
PREVENTIVE MEDICINE REPORTS
(2023)
Review
Allergy
Merlijn van Breugel, Rudolf S. N. Fehrmann, Marnix Buegel, Faisal I. Rezwan, John W. Holloway, Martijn C. Nawijn, Sara Fontanella, Adnan Custovic, Gerard H. Koppelman
Summary: The field of medicine is increasingly interested in artificial intelligence (AI), which allows for new research questions and analysis of larger and different types of data. However, there are few applications of AI in the field of allergy that go beyond proof of concepts and provide clinical value. This review provides an understanding of AI concepts, discusses limitations and challenges such as data availability and bias, and explores potential directions to overcome them. It also presents case examples of AI applications in allergy, with a focus on diagnosis and subtyping. The review shares guidelines for good AI practice, prospects for field advancement, and initiatives to increase clinical impact, highlighting the potential of AI in deepening our understanding of disease mechanisms and contributing to precision medicine in allergy.
Review
Oncology
Keris Poelhekken, Yixuan Lin, Marcel J. W. Greuter, Bert van der Vegt, Monique Dorrius, Geertruida H. de Bock
Summary: The purpose of this review is to identify and analyze the assumptions made in modeling studies on the natural history of DCIS in women in order to improve estimates of overdiagnosis. The most important assumptions include the addition of non-progressive DCIS, classification of DCIS into three grades, and regression possibilities depending on age and grade. Other risk factors for progression of DCIS to IBC were also identified.
Article
Oncology
Sarah Pringle, Floris J. Bikker, Wouter Vogel, Bernadette S. de Bakker, Ingrid Hofland, Bert van der Vegt, Hendrika Bootsma, Frans Kroese, Arjan Vissink, Matthijs Valstar
Summary: Based on histological and immunohistochemical analyses, the tubarial glands resemble salivary glands in terms of tissue and cellular expression, specifically resembling the palatal and labial glands.
RADIOTHERAPY AND ONCOLOGY
(2023)
Article
Multidisciplinary Sciences
Jaron G. de Wit, Jasper Vonk, Floris J. Voskuil, Sebastiaan A. H. J. de Visscher, Kees-Pieter Schepman, Wouter T. R. Hooghiemstra, Matthijs D. Linssen, Sjoerd G. Elias, Gyorgy B. Halmos, Boudewijn E. C. Plaat, Jan J. Doff, Eben L. Rosenthal, Dominic Robinson, Bert van der Vegt, Wouter B. Nagengast, Gooitzen M. van Dam, Max J. H. Witjes
Summary: Using tumor-specific fluorescent tracers, fluorescence molecular imaging (FMI) can accurately visualize tumor tissues. This study evaluated the diagnostic accuracy of an EGFR-targeted FMI for intraoperative margin assessment in oral squamous cell carcinoma patients. The results showed that FMI with cetuximab-800CW had high sensitivity and specificity in detecting tumor-positive margins, providing a safe method for intraoperative adjustment of surgical margins.
NATURE COMMUNICATIONS
(2023)
Article
Oncology
Martine Froukje van der Kamp, Eric Hiddingh, Julius de Vries, Boukje Annemarie Cornelia van Dijk, Ed Schuuring, Lorian Slagter-Menkema, Bert van der Vegt, Gyorgy Bela Halmos
Summary: There is often a discrepancy between the chronological and biological age of head and neck cancer patients. Treatment is based on chronological age, but biological age may be a more accurate predictor of treatment tolerability. This study examined the association between tumor characteristics and chronological and biological age, as well as their relation to survival. The findings suggest that biological age may have a stronger impact on the tumor microenvironment than chronological age, highlighting the importance of investigating treatment response based on biological age.
Article
Oncology
Pieter F. van den Berg, Joseph Pierre Aboumsallem, Elles M. Screever, Canxia Shi, Sanne de Wit, Valentina Bracun, Laura I. Yousif, Lotte Geerlings, Dongyu Wang, Jennifer E. Ho, Stephan J. L. Bakker, Bert van der Vegt, Herman H. W. Sillje, Rudolf A. de Boer, Wouter C. Meijers
Summary: The fibrosis-related biomarker galectin-3 (gal-3) is associated with new-onset cancer and heart failure (HF) in males, but not in females.
JACC: CARDIOONCOLOGY
(2023)
