Article
Oncology
Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T. Lei, Meggie N. Young, Matthew V. Holt, Diana Fandino, Craig T. Vollert, Purba Singh, Mohammad A. Alzubi, Anna Malovannaya, Lacey E. Dobrolecki, Michael T. Lewis, Shunqiang Li, Charles E. Foulds, Matthew J. Ellis
Summary: Transcriptionally active ESR1 fusions (ESR1-TAF) are a major cause of endocrine therapy resistance in breast cancer. By using mass spectrometry, druggable kinases associated with ESR1-TAF were identified, and RET kinase was validated as a common therapeutic target. Inhibition of RET kinase effectively inhibited the growth of breast cancer tumors carrying ESR1-TAF.
Article
Oncology
Xuxu Gou, Beom-Jun Kim, Meenakshi Anurag, Jonathan T. Lei, Meggie N. Young, Matthew V. Holt, Diana Fandino, Craig T. Vollert, Purba Singh, Mohammad A. Alzubi, Anna Malovannaya, Lacey E. Dobrolecki, Michael T. Lewis, Shunqiang Li, Charles E. Foulds, Matthew J. Ellis
Summary: Transcriptionally active ESR1 fusions are a common cause of breast cancer endocrine therapy resistance. This study identifies RET kinase as a potential therapeutic target for ESR1-TAF-driven ET-resistant breast cancer through kinome analysis and drug sensitivity studies.
Article
Oncology
Ganglong Yang, Chenyang Zuo, Yuxiang Lin, Xiaoman Zhou, Piaopiao Wen, Chairui Zhang, Han Xiao, Meichen Jiang, Morihisa Fujita, Xiao-Dong Gao, Fangmeng Fu
Summary: This study explores the molecular characteristics and the relationship between invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) subtypes in luminal A subgroup of breast cancer using proteomics and phosphoproteomics analysis. The results show that the phosphorylation level of proteins in ILC tissues is higher than in IDC tissues. Histone H1.10 is significantly increased in IDC but decreased in ILC, while complement C4-B and Crk-like protein are significantly decreased in IDC but increased in ILC. Furthermore, specific protein expression and phosphorylation changes can clearly distinguish IDC from ILC. The research provides insights for drug development and targeted treatment.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemical Research Methods
Weili Miao, David Bade, Yinsheng Wang
Summary: The study utilized SILAC and PRM methods to investigate the differential expression of kinases in breast cancer cells, revealing that the differentially expressed kinase TAF9 enhances radioresistance in breast cancer cells and plays a role in upregulating genes associated with radioresistance.
JOURNAL OF PROTEOME RESEARCH
(2021)
Article
Oncology
Clemens Hinterleitner, Yanjun Zhou, Claudia Tandler, Jonas S. Heitmann, Korbinian N. Kropp, Martina Hinterleitner, Andre Koch, Andreas D. Hartkopf, Lars Zender, Helmut R. Salih, Stefanie Maurer
Summary: The study shows that TACI expression on platelets is significantly increased in breast cancer patients and correlates with tumor progression, making it a potential prognostic marker for breast cancer.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Yanjun Zhou, Jonas S. Heitmann, Kim L. Clar, Korbinian N. Kropp, Martina Hinterleitner, Tobias Engler, Andre Koch, Andreas D. Hartkopf, Lars Zender, Helmut R. Salih, Stefanie Maurer, Clemens Hinterleitner
Summary: Studies have shown that platelets from cancer patients have higher levels of GITRL, which is specifically regulated during tumor progression by clinical parameters. This indicates that platelets modulate the GITR/GITRL immune checkpoint in the context of malignant disease and provide a rationale for further research into using this axis for immunotherapeutic intervention in cancer patients.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2021)
Article
Multidisciplinary Sciences
Hao Huang, Jianyang Hu, Alishba Maryam, Qinghua Huang, Yuchen Zhang, Saravanan Ramakrishnan, Jingyu Li, Haiying Ma, Victor W. S. Ma, Wah Cheuk, Grace Y. K. So, Wei Wang, William C. S. Cho, Liang Zhang, Kui Ming Chan, Xin Wang, Y. Rebecca Chin
Summary: Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. This study characterizes super-enhancer heterogeneity and identifies genes specifically regulated by TNBC-specific super-enhancers, including FOXC1, MET, and ANLN.
NATURE COMMUNICATIONS
(2021)
Article
Oncology
Sarah Ouahoud, Rutger J. Jacobs, Maikel P. Peppelenbosch, G. M. Fuhler, Jarom Heijmans, Sander Diks, Manon E. Wildenberg, Lucas J. A. C. Hawinkels, Liudmila L. Kodach, Philip W. Voorneveld, James C. H. Hardwick
Summary: This study reveals that statins induce BMP-specific activation of PTEN and inhibit PI3K/Akt/mTOR signaling in CRC. The effects of statins on cell signaling are specific and can be distinguished from nonspecific, toxic effects. Experiments in xenografts and in patients treated with Simvastatin confirm the activation of the BMP pathway, PTEN, and downregulation of mTOR signaling.
BRITISH JOURNAL OF CANCER
(2021)
Article
Oncology
Chia-Che Chang, Chien-Chih Chiu, Pei-Feng Liu, Chih-Hsuan Wu, Yen-Chiang Tseng, Cheng-Hsin Lee, Chih-Wen Shu
Summary: The study identified DYRK1B as a potential gene essential for cell proliferation and mobility of triple-negative breast cancer (TNBC) cells, particularly in those with high DYRK1B expression, which was associated with poor overall survival. CCDC97 and ZNF581 were positively correlated with DYRK1B expression. The results suggest DYRK1B as a potential therapeutic target for TNBC patients.
Article
Engineering, Biomedical
Young Kim, Le Thi Hong Tram, Kyung Ah Kim, Byoung Choul Kim
Summary: Cancer metastasis is influenced by chemical factors and physical cues, particularly mechanical tension of integrins and physical confinement. A microconfinement tension gauge platform is developed to monitor spatial integrin tension in metastatic breast cancer cells. The results reveal that the cells exert the strongest integrin tension at the leading edges during migration on a planar surface, while the tension increases at the cell rear when entering microconfinement. The findings identify the mechanical interactions between integrin tension and microenvironment as a key mechanism for cancer invasion and metastasis.
ADVANCED HEALTHCARE MATERIALS
(2023)
Review
Pathology
Suzan F. Ghannam, Catrin Sian Rutland, Cinzia Allegrucci, Nigel P. Mongan, Emad Rakha
Summary: Basement membrane (BM) is an important structure separating the epithelium from the stroma, and its composition varies during different stages of breast development. In pathological conditions, the presence or absence of BM plays a crucial role in distinguishing in situ from invasive lesions. Although diagnostic techniques are evolving, BM is still considered a useful marker in ambiguous cases. This review discusses the structure, function, and clinical significance of BM in relation to breast lesions, with a focus on differentiating it from alternative pathological tissue.
JOURNAL OF CLINICAL PATHOLOGY
(2023)
Article
Pathology
Asmaa Ibrahim, Ayat G. Lashen, Ayaka Katayama, Raluca Mihai, Graham Ball, Michael S. Toss, Emad A. Rakha
Summary: Counting mitoses is an important part of breast cancer grading, but studies have shown low agreement in current practices. This study aimed to refine the methodology for optimal mitoses counting on whole slide images (WSIs), with the most significant parameter for identifying hotspots being the relative increase in tumor cell density. Counting mitoses in a 3 mm(2) area was found to be the most representative and reliable, while using multiple digital high-power screen fields (HPSFs) provided the most reliable and practical method for mitoses counting on WSI. Adjusting the number of monitor screens can help perform visual mitoses scoring reliably.
Review
Biochemistry & Molecular Biology
Maria Luisa Sanchez-Leon, Carlos Jimenez-Cortegana, Silvia Silva Romeiro, Carmen Garnacho, Luis de la Cruz-Merino, Daniel J. Garcia-Dominguez, Lourdes Hontecillas-Prieto, Victor Sanchez-Margalet
Summary: Breast cancer is the most diagnosed tumor in women with diverse molecular profiles. Despite the advancements in early detection and therapy, patients with metastatic disease have low survival rates. Immunotherapy, due to its ability to modulate the immune system, has emerged as a promising alternative. This review focuses on the new immunotherapies in breast cancer in the last five years and discusses the role of myeloid-derived suppressor cells as a therapeutic target.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Haitao Zhang, Xiaolei Cao, Mei Tang, Guoxuan Zhong, Yuan Si, Haidong Li, Feifeng Zhu, Qinghua Liao, Liuju Li, Jianhui Zhao, Jia Feng, Shuaifeng Li, Chenliang Wang, Manuel Kaulich, Fangwei Wang, Liangyi Chen, Li Li, Zongping Xia, Tingbo Liang, Huasong Lu, Xin-Hua Feng, Bin Zhao
Summary: The human kinome consists of 538 kinases that play essential roles in catalyzing protein phosphorylation. The annotation and visualization of the subcellular distribution of these kinases in the Kinome Atlas (KA) provide insights into their functions and mechanisms, including new kinase localizations and the role of liquid-liquid phase separation in kinase condensate formation. Despite limitations such as potential mislocalization, the subcellular map of the kinome can be utilized to enhance our understanding of regulatory mechanisms involving protein phosphorylation.
Review
Pharmacology & Pharmacy
Deep Rohan Chatterjee, Saumya Kapoor, Meenakshi Jain, Rudradip Das, Moumita Ghosh Chowdhury, Amit Shard
Summary: The development of proteolysis-targeting chimeras (PROTACs) has led to the discovery of drugs that specifically target undruggable proteins. Small molecule-based PROTACs that target intracellular pathways have entered clinical trials, and their combination with antibodies has shown potent effects in cancer treatment. This review discusses the recent milestones and challenges in this area of drug development, as well as the best path forward.
DRUG DISCOVERY TODAY
(2023)
Article
Cell Biology
Fabio L. Urbina, Shawn M. Gomez, Stephanie L. Gupton
JOURNAL OF CELL BIOLOGY
(2018)
Correction
Biotechnology & Applied Microbiology
Tudor I. Oprea, Cristian G. Bologa, Soren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Steven L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schurer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dusica Vidovic, Anna Waller, David Westergaard, Jeremy J. Yang, Gergely Zahoranszky-Kohalmi
NATURE REVIEWS DRUG DISCOVERY
(2018)
Article
Biotechnology & Applied Microbiology
Tudor I. Oprea, Cristian G. Bologa, Soren Brunak, Allen Campbell, Gregory N. Gan, Anna Gaulton, Shawn M. Gomez, Rajarshi Guha, Anne Hersey, Jayme Holmes, Ajit Jadhav, Lars Juhl Jensen, Gary L. Johnson, Anneli Karlson, Andrew R. Leach, Avi Ma'ayan, Anna Malovannaya, Subramani Mani, Stephen L. Mathias, Michael T. McManus, Terrence F. Meehan, Christian von Mering, Daniel Muthas, Dac-Trung Nguyen, John P. Overington, George Papadatos, Jun Qin, Christian Reich, Bryan L. Roth, Stephan C. Schurer, Anton Simeonov, Larry A. Sklar, Noel Southall, Susumu Tomita, Ilinca Tudose, Oleg Ursu, Dusica Vidovic, Anna Waller, David Westergaard, Jeremy J. Yang, Gergely Zahoranszky-Kohalmi
NATURE REVIEWS DRUG DISCOVERY
(2018)
Article
Biochemistry & Molecular Biology
Matthew E. Berginski, Nienke Moret, Changchang Liu, Dennis Goldfarb, Peter K. Sorger, Shawn M. Gomez
Summary: Kinases play crucial roles in cell signaling pathways, with known dysfunctions being linked to various pathologies. However, the functions of nearly one-third of kinases remain largely unknown. The Dark Kinase Knowledgebase (DKK) aims to provide data and reagents for these understudied kinases, supporting the broader research community in exploring potentially high-impact druggable targets.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Engineering, Biomedical
Sebastian Mestril, Raehyun Kim, Samuel S. Hinman, Shawn M. Gomez, Nancy L. Allbritton
Summary: The study demonstrated that colonic epithelial cultures enriched for stem/proliferative cells exhibit higher frequency and shorter pulse width of Ca2+ transients, and differentiation leads to a decrease in transient frequency by 50% and an increase in pulse width by 200%. Various metabolites and growth factors can modulate Ca2+ oscillation patterns consistently, while increasing the stiffness of the supportive matrix shifts Ca2+ transient patterns toward those resembling differentiated cells.
ADVANCED HEALTHCARE MATERIALS
(2021)
Article
Biochemical Research Methods
Kathryn E. Kirchoff, Shawn M. Gomez
Summary: Motivation: Phosphorylation is crucial for cellular signaling, but the specific kinases involved in phosphorylation events are largely unknown. This study presents a deep learning method, EMBER, that integrates kinase phylogenetic information and motif-dissimilarity information to predict kinase-motif phosphorylation events, improving the known map of phosphorylation relationships.
Article
Biochemistry & Molecular Biology
Rex E. Jeffries, Shawn M. Gomez, Jeffrey M. Macdonald, Michael P. Gamcsik
Summary: Nuclear magnetic resonance (NMR) spectroscopy was used to monitor the metabolism of glutathione in alginate-encapsulated JM-1 hepatoma cells. The results showed that the C-13-labeled glutathione signal provided a high-intensity spectrum, allowing for the monitoring of the detailed kinetics of glutathione metabolism. Additionally, the effects of the thiol alkylating agent on glutathione metabolism were observed, and the regeneration of intracellular glutathione was studied through the restoration of the C-13-glutathione signal and the wash-out of the conjugate.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Kevin A. Chen, Matthew E. Berginski, Chirag S. Desai, Jose G. Guillem, Jonathan Stem, Shawn M. Gomez, Muneera R. Kapadia
Summary: This study developed and compared deep neural network (NN) models and logistic regression (LR) models for predicting complications after colectomy, hepatectomy, and pancreaticoduodenectomy (PD). The results showed that machine learning models had a slight advantage over traditional statistical techniques in predicting procedure-specific outcomes, and models that included intra-operative information performed better.
JOURNAL OF GASTROINTESTINAL SURGERY
(2022)
Article
Gastroenterology & Hepatology
Kevin A. Chen, Chinmaya U. Joisa, Karyn B. Stitzenberg, Jonathan Stem, Jose G. Guillem, Shawn M. Gomez, Muneera R. Kapadia
Summary: Machine learning approaches have shown superiority in predicting readmission after colorectal surgery compared to traditional statistical methods.
JOURNAL OF GASTROINTESTINAL SURGERY
(2022)
Article
Gastroenterology & Hepatology
Kevin A. Chen, Chinmaya U. Joisa, Jonathan M. Stem, Jose G. Guillem, Shawn M. Gomez, Muneera R. Kapadia
Summary: This study used machine learning techniques to develop a more accurate predictive model for colorectal surgical-site infections. Compared to logistic regression, machine learning showed higher accuracy. These techniques can be used to identify high-risk patients and target preventive interventions for surgical-site infection.
DISEASES OF THE COLON & RECTUM
(2023)
Article
Surgery
Kevin A. Chen, Chinmaya U. Joisa, Jonathan M. Stem, Jose G. Guillem, Shawn M. Gomez, Muneera R. Kapadia
Summary: Machine learning models showed higher accuracy in predicting ureteral injury during colorectal surgery compared to logistic regression and previous models, which can support decision making regarding preoperative ureteral stent placement.
Article
Surgery
Logan R. Butler, Kevin A. Chen, Justin Hsu, Muneera R. Kapadia, Shawn M. Gomez, Timothy M. Farrell
Summary: Machine learning algorithms outperform logistic regression in predicting readmissions following bariatric surgery, offering higher accuracy and discrimination. The application of these models can help identify candidates for early discharge or targeted postdischarge resources.
SURGERY FOR OBESITY AND RELATED DISEASES
(2023)
Article
Biochemical Research Methods
Matthew Berginski, Chinmaya Joisa, Brian Golitz, Shawn Gomez
Summary: Protein kinases are important in cellular processes, and compounds inhibiting their activity are a focus in targeted therapy development, particularly in cancer. This study combines kinase inhibitor profiles and gene expression data to predict cell viability screening results, achieving high prediction accuracy. The results demonstrate that knowledge of the kinome can predict specific cell phenotypes, and can be integrated into targeted therapy development.
PLOS COMPUTATIONAL BIOLOGY
(2023)
Article
Oncology
Kevin A. Chen, Kathryn E. Kirchoff, Logan R. Butler, Alexa D. Holloway, Muneera R. Kapadia, Cherie M. Kuzmiak, Stephanie M. Downs-Canner, Phillip M. Spanheimer, Kristalyn K. Gallagher, Shawn M. Gomez
Summary: An artificial intelligence model was developed to predict the pathologic margin status of resected breast tumors using specimen mammography. The model showed high accuracy and potential to guide the extent of resection, improving cosmesis and reducing reoperations.
ANNALS OF SURGICAL ONCOLOGY
(2023)
Article
Gastroenterology & Hepatology
Kevin A. Chen, Paolo Goffredo, David Hu, Chinmaya U. Joisa, Jose G. Guillem, Shawn M. Gomez, Muneera R. Kapadia
Summary: Machine learning-based models were developed to predict outcomes in anal squamous cell carcinoma (ASCC), showing higher accuracy compared to logistic regression for locoregional failure. These models may assist clinicians in identifying high-risk ASCC patients after external validation.
JOURNAL OF GASTROINTESTINAL SURGERY
(2023)
