Article
Biochemistry & Molecular Biology
Blake R. Rushing
Summary: Drug resistance is a significant problem in cancer therapy, and there is still much to be learned about its molecular underpinnings. This study used a multi-omics approach to investigate the molecular networks and metabolic processes that differentiate cancer cells sensitive or resistant to antifolates, a commonly used class of anticancer drugs. The results provide new insights into the mechanisms of intrinsic antifolate resistance and may inform the development of novel therapeutic strategies and personalized treatment approaches.
Article
Oncology
Julia Krushkal, Simarjeet Negi, Laura M. Yee, Jason R. Evans, Tanja Grkovic, Alida Palmisano, Jianwen Fang, Hari Sankaran, Lisa M. McShane, Yingdong Zhao, Barry R. O'Keefe
Summary: Investigation revealed associations between gene expression and the response of cancer cells to specific categories of natural products, suggesting potential mechanisms of action and paving the way for future targeted cancer chemotherapy agent discovery and design.
MOLECULAR ONCOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Evangelia Sereti, Chrisiida Tsimplouli, Elisavet Kalaitsidou, Nikos Sakellaridis, Konstantinos Dimas
Summary: This study aimed to investigate the expression levels of both sigma receptor subtypes in several human cancer cell lines and study their relationship with the activity of sigma ligands. Through in vitro experiments and the NCI60 COMPARE algorithm, the cytotoxic mechanism of action of the selected sigma ligands studied herein was further elucidated.
Article
Oncology
Hari Sankaran, Simarjeet Negi, Lisa M. McShane, Yingdong Zhao, Julia Krushkal
Summary: This study analyzed the activity of Indian natural products in the NCI-60 cell line panel and identified associations with gene expression and mutations related to cancer treatment. The findings are important for understanding the mechanisms of these Indian natural products.
Review
Biochemistry & Molecular Biology
Sarah Jane Annesley, Paul Robert Fisher
Summary: The study of mitochondrial function in neurological disorders is challenging due to the inaccessibility of brain tissue, but the use of lymphoblastoid cell lines (LCLs) is an effective approach. These cell models can help understand mitochondrial defects, signaling pathways, and biomarkers in neurological disorders, and are valuable for the development of diagnostic tests and identification of drug targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Paul Workman
Summary: The NCI-60 screen, which involved screening of 10,000 diverse compounds against 60 human tumor cell lines, marked a major technological advance in cancer research and development. It provided the foundation for subsequent larger-scale human cancer cell panel screens with detailed molecular annotation and sophisticated informatics, enabling the implementation of modern molecular target-based drug discovery and precision oncology.
Article
Biochemistry & Molecular Biology
Blake R. Rushing
Summary: This study used a multi-omics approach to explore the molecular determinants affecting the response of cancer cells to alkylating agents. Through integrated pathway analysis, key metabolic pathways were identified, and potential druggable targets were revealed. Copy number variant analysis also identified notable differences in genes associated with metabolic changes, protein trafficking, and miRNAs between drug-sensitive and drug-resistant cells. These findings provide a comprehensive view of the molecular landscape underlying the response to alkylating agents and can contribute to the development of personalized treatment strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biology
Elliott D. SoRelle, Joanne Dai, Emmanuela N. Bonglack, Emma M. Heckenberg, Jeffrey Y. Zhou, Stephanie N. Giamberardino, Jeffrey A. Bailey, Simon G. Gregory, Cliburn Chan, Micah A. Luftig
Summary: The study characterized single-cell transcriptomic profiles of five LCLs, revealing substantial phenotypic heterogeneity within and across LCLs likely due to intrinsic variance in primary B cells and host-pathogen dynamics. Stochastic simulations demonstrate that factors such as initial primary cell heterogeneity, random sampling, time in culture, and phenotype-specific fitness differences can contribute substantially to dynamic diversity in populations of nominally clonal cells.
Article
Biology
Chaymae Ziyani, Olivier Delaneau, Diogo M. Ribeiro
Summary: Non-coding regulatory elements, such as enhancers, play a key role in controlling the cell-type specificity and spatio-temporal expression of genes. By using single cell technology to assess chromatin status and gene expression in the same cells, we found that enhancers targeting the same gene often display simultaneous activity and share similar transcription factor binding profiles. Furthermore, we predicted significant enhancer-enhancer associations and found that co-active enhancers are more likely to be bound by similar transcription factors.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Chunyu Liu, Jessica L. Fetterman, Xianbang Sun, Kaiyu Yan, Poching Liu, Yan Luo, Jun Ding, Jun Zhu, Daniel Levy
Summary: This study compared mtDNA sequence variants between LCL and whole blood samples. The results showed that most homoplasmic variants were present in both LCL and blood samples, while most heteroplasmic variants were unique to either LCL or blood samples. LCL samples had a higher number of heteroplasmic variants compared to whole blood samples, but a similar number of homoplasmic variants. Additionally, LCL samples tended to have lower levels of heteroplasmy.
SCIENTIFIC REPORTS
(2022)
Article
Pharmacology & Pharmacy
Yu-Lin Kuang, Elizabeth Theusch, Ronald M Krauss, Marisa W Medina
Summary: Statins have varying efficacy in reducing low-density lipoprotein levels and cardiovascular disease risk among individuals, with a small but significant risk of adverse effects such as myopathy and diabetes. Identifying biomarkers to predict patients who would benefit most from statin treatment without increasing risk of side effects could have a significant impact on public health. This review discusses the use of lymphoblastoid cell lines in studying statin pharmacogenomics and different approaches to identify genetic markers associated with individual differences in statin response.
Article
Biotechnology & Applied Microbiology
Farida S. Akhtari, Tammy M. Havener, Daniel L. Hertz, Jeremy Ash, Alexandra Larson, Lisa A. Carey, Howard L. McLeod, Alison A. Motsinger-Reif
Summary: The study found significant associations between race and smoking status with ex-vivo dose-response in LCLs from breast cancer patients, suggesting that in-vivo smoking status may influence ex-vivo dose-response. More precise measures of covariates can improve forecasting of clinical effect in cancer therapeutics.
PHARMACOGENETICS AND GENOMICS
(2021)
Article
Biochemistry & Molecular Biology
Danielle Whitham, Eugene Belenkiy, Costel C. C. Darie, Aurelian Radu
Summary: Lymphoblastoid cell lines (LCLs) are ideal for studying ALS, and proteomics analysis using liquid chromatography followed by tandem mass spectrometry can identify differentially expressed proteins and cellular pathways in ALS compared to healthy controls. This provides a promising approach for further investigating ALS mechanisms and searching for therapeutic agents.
Article
Multidisciplinary Sciences
Oscar L. Rodriguez, Andrew J. Sharp, Corey T. Watson
Summary: Lymphoblastoid cell lines (LCLs) are crucial for genetic research, but V(D)J recombination has shown impacts on short read sequencing data from LCLs.
Article
Biochemistry & Molecular Biology
Liron Mizrahi, Ashwani Choudhary, Polina Ofer, Gabriela Goldberg, Elena Milanesi, John R. Kelsoe, David Gurwitz, Martin Alda, Fred H. Gage, Shani Stern
Summary: Bipolar disorder is a mood disorder characterized by recurrent episodes of mania and depression. Many patients do not respond to the first-line treatment drug lithium, making clinical management challenging. By analyzing gene expression in lymphoblastoid cell lines, we identified potential biomarkers for diagnosing and treating bipolar disorder. We also developed machine learning algorithms that accurately predicted lithium response in different patient cohorts. This methodology shows promise for guiding therapeutic interventions.
MOLECULAR PSYCHIATRY
(2023)