Review
Biochemical Research Methods
Fangfang Xia, Jonathan Allen, Prasanna Balaprakash, Thomas Brettin, Cristina Garcia-Cardona, Austin Clyde, Judith Cohn, James Doroshow, Xiaotian Duan, Veronika Dubinkina, Yvonne Evrard, Ya Ju Fan, Jason Gans, Stewart He, Pinyi Lu, Sergei Maslov, Alexander Partin, Maulik Shukla, Eric Stahlberg, Justin M. Wozniak, Hyunseung Yoo, George Zaki, Yitan Zhu, Rick Stevens
Summary: To enable personalized cancer treatment, machine learning models have been developed to predict drug response based on tumor and drug features. This study used machine learning to analyze five publicly available cell line-based data sets and rigorously evaluated the model generalizability between different studies. The results showed that a multitasking deep neural network achieved the best cross-study generalizability, with models trained on the CTRP data set providing the most accurate predictions on testing data, and the gCSI data set being the most predictable among the cell line data sets.
BRIEFINGS IN BIOINFORMATICS
(2022)
Article
Biochemistry & Molecular Biology
Vinitha Richard, Madhumathy G. G. Nair, Vishnu S. S. Jaikumar, Sara Jones, Jyothi S. S. Prabhu, Michael J. J. Kerin
Summary: Luminal breast cancer subtypes respond poorly to endocrine and trastuzumab treatments due to cellular heterogeneity arising from the loss of receptor expression. The origins of basal-like and HER2-overexpressing breast cancer subtypes have been attributed to genetic and protein modifications in stem-like cells and luminal progenitor cell populations, respectively. This study aims to identify the fractions of luminal breast cancer cells that share stemness potentials and marker profiles and to elucidate the molecular regulatory mechanism that drives transitions between fractions, leading to receptor discordances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
Emanuel Goncalves, Rebecca C. Poulos, Zhaoxiang Cai, Syd Barthorpe, Srikanth S. Manda, Natasha Lucas, Alexandra Beck, Daniel Bucio-Noble, Michael Dausmann, Caitlin Hall, Michael Hecker, Jennifer Koh, Howard Lightfoot, Sadia Mahboob, Iman Mali, James Morris, Laura Richardson, Akila J. Seneviratne, Rebecca Shepherd, Erin Sykes, Frances Thomas, Sara Valentini, Steven G. Williams, Yangxiu Wu, Dylan Xavier, Karen L. MacKenzie, Peter G. Hains, Brett Tully, Phillip J. Robinson, Qing Zhong, Mathew J. Garnett, Roger R. Reddel
Summary: The study analyzes the proteomes of multiple cancer cell lines through mass spectrometry and reveals thousands of cancer protein biomarkers that are not significant at the transcript level, demonstrating that the proteome has predictive power for drug response similar to the transcriptome.
Article
Multidisciplinary Sciences
G. Gambardella, G. Viscido, B. Tumaini, A. Isacchi, R. Bosotti, D. di Bernardo
Summary: This study characterizes the cell lines of different subtypes of breast cancer using single-cell RNA-seq and trains a deconvolution algorithm to predict drug responses in heterogeneous tumor cell populations. The findings show high heterogeneity in the expression of biomarkers within cancer cells, and transcriptional heterogeneity allows cells with differential drug sensitivity to coexist in the same population. This work provides a framework to determine tumor heterogeneity in terms of cell line composition and drug response.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Amal Ahmed Mohamed, Ahmed E. Allam, Ahmed M. Aref, Maha Osama Mahmoud, Noha A. Eldesoky, Naglaa Fawazy, Yasser Sakr, Mohamed Emam Sobeih, Sarah Albogami, Eman Fayad, Fayez Althobaiti, Ibrahim Jafri, Ghadi Alsharif, Marwa El-Sayed, Asmaa Sayed Abdelgeliel, Rania S. Abdel Aziz
Summary: This study evaluated the use of serum microRNAs (miRs) as biomarkers for early detection of breast cancer (BC) in Egyptian patients. The results showed that miR-155, miR-373, and miR-10b were upregulated, while miR-34a was downregulated in nonmetastatic BC patients. miR-155 and miR-10b were correlated with tumor size and nodal involvement. The combination of these miRs showed high sensitivity and specificity for BC detection.
Article
Genetics & Heredity
Edward Simpson, Steven Chen, Jill L. Reiter, Yunlong Liu
Summary: This study evaluated the potential of using basal-level splicing information to predict drug sensitivity by constructing classification models with splicing and expression data. The researchers detailed splicing differences between sensitive and resistant cell lines, identified altered inclusion of 277 skipped exons, and characterized potential cis- and trans-acting elements influencing doxorubicin response. The results showed a strong predictive power of the classification model built with skipped exon data, revealing an association with epithelial-mesenchymal transition and differential expression of RBFOX and ELAVL RBP family members.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2021)
Article
Multidisciplinary Sciences
Han Jin, Cheng Zhang, Martin Zwahlen, Kalle von Feilitzen, Max Karlsson, Mengnan Shi, Meng Yuan, Xiya Song, Xiangyu Li, Hong Yang, Hasan Turkez, Linn Fagerberg, Mathias Uhlen, Adil Mardinoglu
Summary: In this study, the expression of all human protein-coding genes in over 1,000 human cell lines representing 27 cancer types was investigated using a genome-wide transcriptomics analysis. The authors compared the cell line gene expression with the corresponding profiles in various tissues, organs, single-cell types, and cancers, and provided guidance for selecting the most appropriate cell line for experimental studies. Additionally, they explored the cancer-related pathway and cytokine activity of the cell lines to aid in human biology studies and drug development projects.
NATURE COMMUNICATIONS
(2023)
Review
Instruments & Instrumentation
Fahima Danesh Pouya, Yousef Rasmi, Maria Gazouli, Eleni Zografos, Mohadeseh Nemati
Summary: MicroRNAs play a crucial role in the development and progression of breast cancer, with their expression patterns serving as indicators of metastatic potential. The identification of key microRNAs could lead to the development of novel therapeutic molecules, while an efficient delivery system is essential for microRNA-based therapies.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Biochemical Research Methods
Min Li, Yake Wang, Ruiqing Zheng, Xinghua Shi, Yaohang Li, Fang-Xiang Wu, Jianxin Wang
Summary: In this study, a deep learning model called DeepDSC was developed to predict drug sensitivity by integrating genomic features and chemical information. The performance of the model was demonstrated through 10-fold cross-validation on the CCLE and GDSC datasets, showing high prediction accuracy.
IEEE-ACM TRANSACTIONS ON COMPUTATIONAL BIOLOGY AND BIOINFORMATICS
(2021)
Article
Biochemistry & Molecular Biology
Katherine Ellis, Rachael Wood
Summary: The objective of this study was to compare the invasiveness of three available endometriotic cell lines to cancer cell lines and assess consistency across different invasion assays. The results showed that the endometriotic cell lines exhibited similar invasiveness to the cancer cell lines and there were no significant differences. The expression of E-Cadherin declined in the invaded EEC12Z cells, supporting the hypothesis of epithelial-to-mesenchymal transition influencing the invasiveness of peritoneal endometriosis cell line.
Article
Medicine, Research & Experimental
Agnes E. Kulmany, Eva Frank, Dora Kovacs, Kerstin Kirisits, Georg Krupitza, Patricia Neuperger, Robert Alfoldi, Laszlo G. Puskas, Gabor J. Szebeni, Istvan Zupko
Summary: The D-ring-modified exo-heterocyclic androstadiene derivative 17APAD shows high selectivity and superior effects in inhibiting tumor growth and metastasis in human breast cancer-derived cell lines compared to the reference drug cisplatin.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Review
Oncology
Giulia Cosentino, Ilaria Plantamura, Elda Tagliabue, Marilena Iorio, Alessandra Cataldo
Summary: The crosstalk between neoplastic cells and the microenvironment is crucial in tumor development and resistance to anticancer therapies. MicroRNAs play a key role in inducing pro-tumoral traits in stromal cells and fueling tumor aggressiveness. Recent literature highlights the significance of miRNAs in shaping the tumor microenvironment and modulating responsiveness to therapies.
Article
Oncology
V. C. Leeuwenburgh, C. G. Urzua-Traslavina, A. Bhattacharya, M. T. C. Walvoort, M. Jalving, S. de Jong, R. S. N. Fehrmann
Summary: By utilizing consensus independent component analyses on patient-derived tumor biopsies, this study identified 555 robust metabolic transcription components and demonstrated how they can be used to explore associations with drug sensitivities, patient outcomes, and the immune tumor microenvironment. The findings provide a valuable resource for formulating new hypotheses on metabolically engaging tumors or their microenvironments.
CANCER & METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Filippo Acconcia
Summary: The molecular classification of breast cancer determines the treatment options, and ER alpha-positive breast cancer can be treated with various drugs. Cardiac glycosides (CGs) can be repurposed for the treatment of ER alpha-positive breast cancer, but they may need to be combined with other drugs, and the ATP1B3 Na/K ATPase isoform can serve as a biomarker for personalized treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
Marian Kalocsay, Matthew J. Berberich, Robert A. Everley, Maulik K. Nariya, Mirra Chung, Benjamin Gaudio, Chiara Victor, Gary A. Bradshaw, Robyn J. Eisert, Marc Hafner, Peter K. Sorger, Caitlin E. Mills, Kartik Subramanian
Summary: Quantitative proteomics was performed on 60 human-derived breast cancer cell line models, resulting in the identification and characterization of subtypes of breast cancer. The datasets were found to conform to known transcriptional subtypes and are freely available for public use. These datasets can be used in combination with other measurements to predict drug response, provide context in signaling pathway models, and identify markers of sensitivity or resistance to therapeutics.
Article
Oncology
Delal Akdeniz, Mark van Barele, Bernadette A. M. Heemskerk-Gerritsen, Ewout W. Steyerberg, Michael Hauptmann, Irma van de Beek, Klaartje van Engelen, Marijke R. Wevers, Encarnacion B. Gomez Garcia, Margreet G. E. M. Ausems, Lieke P. Berger, Christi J. van Asperen, Muriel A. Adank, Margriet J. Collee, Denise J. Stommel-Jenner, Agnes Jager, Marjanka K. Schmidt, Maartje J. Hooning
Summary: Chemotherapy shows significant risk reduction for contralateral breast cancer in BRCA1 carriers, especially within the first 5 years. Anthracyclines and the combination with taxanes are associated with substantial risk reduction in this population.
Article
Oncology
Anne-Rose W. Schut, Anne L. M. Vriends, Andrea Sacchetti, Milea J. M. Timbergen, Benjamin A. Alman, Mushriq Al-Jazrawe, Dirk J. Grunhagen, Cornelis Verhoef, Stefan Sleijfer, Erik A. C. Wiemer
Summary: This study identified ferroptosis and apoptosis as mechanisms for the sorafenib-induced cell death in DTF cells as well as stromal cells. Furthermore, autophagy inhibition enhanced the cytotoxic effects of sorafenib. Knowledge of the mechanisms by which sorafenib affects DTF at a cellular level may help to optimize its clinical efficacy and mitigate toxic effects.
Review
Immunology
Rakesh Kulkarni, Erik A. C. Wiemer, Wen Chang
Summary: Lipid rafts are important components of cell membranes and play crucial roles in cellular processes and signaling. Both pathogens and hosts utilize lipid rafts to survive and initiate antimicrobial responses. This review focuses on the enrichment of major vault protein in lipid rafts during vaccinia virus infection.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biology
Joe Dennis, Jonathan P. Tyrer, Logan C. Walker, Kyriaki Michailidou, Leila Dorling, Manjeet K. Bolla, Qin Wang, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Natalia Bogdanova, Stig E. Bojesen, Hermann Brenner, Jose E. Castelao, Jenny Chang-Claude, Georgia Chenevix-Trench, Christine L. Clarke, J. Margriet Collee, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dork, Laure Dossus, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat Garcia-Closas, Graham G. Giles, Anna Gonzalez-Neira, Pascal Guenel, Eric Hahnen, Christopher A. Haiman, Per Hall, Antoinette Hollestelle, Reiner Hoppe, John L. Hopper, Anthony Howell, Agnes Jager, Anna Jakubowska, Esther M. John, Nichola Johnson, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Veli-Matti Kosma, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, James Lacey, Diether Lambrechts, Nicole L. Larson, Martha Linet, Alicja Ogrodniczak, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Taru A. Muranen, Rachel A. Murphy, Heli Nevanlinna, Janet E. Olson, Hakan Olsson, Tjoung-Won Park-Simon, Charles M. Perou, Paolo Peterlongo, Dijana Plaseska-Karanfilska, Katri Pylkas, Gad Rennert, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Rana Shibli, Ann Smeets, Penny Soucy, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Ian Tomlinson, Melissa A. Troester, Therese Truong, Celine M. Vachon, Camilla Wendt, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Argyrios Ziogas, Jacques Simard, Alison M. Dunning, Paul D. P. Pharoah, Douglas F. Easton
Summary: This study investigates the potential associations between rare germline copy number variants (CNVs) and breast cancer using a genome-wide analysis in a large breast cancer case-control dataset. The study identifies associations between exonic deletions in established breast cancer susceptibility genes and suggests potential associations for non-coding CNVs in both known and novel loci with large effects sizes.
COMMUNICATIONS BIOLOGY
(2022)
Article
Hematology
Qingling Liu, Junlu Pan, Linrui Bao, Chunxiang Xu, Yu Qi, Bin Jiang, Dongdong Wang, Xudong Zhu, Xiaoyu Li, Hanwen Zhang, Hui Bai, Qing Yang, Junqing Ma, Erik A. C. Wiemer, Jingjing Ben, Qi Chen
Summary: This study found that MVP can attenuate macrophage-associated plaque instability by inhibiting the production of MMP-9 mediated by the ASK1-JNK signaling pathway. This discovery suggests that suppression of macrophage ASK1-JNK signaling may be an effective strategy against atherosclerotic diseases.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2022)
Article
Oncology
Mark van Barele, Amy Rieborn, Bernadette A. M. Heemskerk-Gerritsen, Inge-Marie Obdeijn, Linetta B. Koppert, Claudette E. Loo, Rob A. E. M. Tollenaar, Margreet G. E. M. Ausems, Irma van de Beek, Lieke P. Berger, Maaike de Boer, Liselot P. van Hest, C. Marleen Kets, Matti Rookus, Hebon, Marjanka K. Schmidt, Agnes Jager, Maartje J. Hooning
Summary: Tumor size has prognostic impact on BRCA1/2 mutation carriers with pT1 breast cancer. The study findings suggest that chemotherapy improves overall survival in node-negative patients. Smaller tumor size is associated with better overall survival and less lymph node involvement.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Meeting Abstract
Oncology
Anouk H. Eijkelboom, Sabine Siesling, Linda de Munck, Desiree H. J. G. van den Bongard, Willemien Menke-van der Houven van Oordt, Pieter J. Westenend, Ester J. M. Siemerink, Luc J. A. Strobbe, Marie-Jeanne T. F. D. Vrancken Peeters, Linetta B. Koppert, Marc A. M. Mureau, Agnes Jager, Mireille J. M. Broeders, Marc B. I. Lobbes, Helena M. Verkooijen, Jelle Wesseling, Marjolein Smidt, Vivianne C. G. Tjan-Heijnen
Meeting Abstract
Oncology
Noraly Verschoor, Elisabeth M. Jongbloed, Jaco Kraan, Vanja de Weerd, Ngoc M. Van, Agnes Jager, Stefan Sleijfer, Saskia M. Wilting, John W. M. Martens
Meeting Abstract
Oncology
Marianne Luyendijk, Hedwig Blommestein, Agnes Jager, Sabine Siesling, Carin Uyl-de Groot
Article
Oncology
Nathalie Bouwer, Tessa G. Steenbruggen, Hanah N. Rier, Jos J. E. M. Kitzen, Carolien H. Smorenburg, Marlies L. van Bekkum, Paul C. de Jong, Jan C. Drooger, Cynthia Holterhues, Marcel J. M. Kofflard, Eric Boersma, Gabe S. Sonke, Mark-David Levin, Agnes Jager
Summary: This study investigated the impact of trastuzumab on cardiac function in patients with HER2-positive metastatic breast cancer. The findings showed that despite having a reduced baseline left ventricular ejection fraction, 65% of patients did not develop severe cardiotoxicity during an 18-month follow-up. If severe cardiotoxicity did occur, it was partly reversible in more than two-thirds of the cases.
INTERNATIONAL JOURNAL OF CANCER
(2022)
Article
Biochemistry & Molecular Biology
Ronald O. B. de Keizer, Anne L. M. Vriends, Gijsbert J. Hotte, Dion A. Paridaens, Erik A. C. Wiemer, Robert M. Verdijk
Summary: The study aims to find microRNA biomarkers to distinguish between Ocular Sebaceous Carcinoma (OSC) and Squamous Cell Carcinomas of the Conjunctiva (SCCC), as well as normal tissue. The combination of miR-196b-5p and miR-107 can be used as an additional diagnostic tool to differentiate OSC and SCCC.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Marjolijn M. Ladan, Titia G. Meijer, Nicole S. Verkaik, Zofia M. Komar, Carolien H. M. van Deurzen, Michael A. den Bakker, Roland Kanaar, Dik C. van Gent, Agnes Jager
Summary: This study explores the feasibility of a functional sensitivity test for the chemotherapeutic agents cisplatin and docetaxel on breast cancer tissue slices in culture. The results show that these two agents need to be analyzed differently and the test has been adapted for biopsies from metastatic breast tumors. The test is now ready for evaluation of its predictive value in clinical trials.
Article
Immunology
Yan Yang, Na Zhao, Ruobing Wang, Zhuorong Zhan, Shuyu Guo, Haiyang Song, Erik A. C. Wiemer, Jingjing Ben, Junqing Ma
Summary: This study revealed that major vault protein (MVP) plays a crucial role in macrophage polarization during fracture repair. The lack of MVP impairs the inflammatory state transition of macrophages, resulting in impaired fracture repair.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Cell Biology
Ruobing Wang, Yan Yang, Zhongyin Zhang, Na Zhao, Erik A. C. Wiemer, Jingjing Ben, Junqing Ma, Lichan Yuan
Summary: A decline of MVP in osteoclasts with aging was observed, and conditional knockout of MVP inhibited osteoclast apoptosis in vivo and in vitro. The interaction between MVP and death receptor Fas was reported, and the MVP-Fas signaling cascade was identified to positively regulate the apoptosis of osteoclasts, thus preventing osteoporosis.
CELL DEATH & DISEASE
(2023)
Article
Oncology
Stefan A. J. Buck, C. Louwrens Braal, Maaike M. Hofman, Esther Oomen-de Hoop, Peter de Bruijn, Inge M. Ghobadi Moghaddam-Helmantel, Koen G. A. M. Hussaarts, Mijntje B. Vastbinder, Quirine C. Van Rossum-Schornagel, Ron H. N. van Schaik, Agnes Jager, Stijn L. W. Koolen, Ron H. J. Mathijssen
Summary: Combining probenecid with tamoxifen can effectively increase the concentration of endoxifen in breast cancer patients, providing a solution for patients who have poor metabolism or low endoxifen concentrations despite earlier tamoxifen treatment.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2022)