The structure of DNA is wondrously appealing in its elegant simplicity combined with its captivating power. The power of DNA derives directly from, and solely from, the fact that it represents digital information. However, this delightful digital determinism does not carry over into the multitude of cellular processes, especially in a cancer cell. This means that the sequencing of the human genome has some limitations regarding furthering the understanding of details of cancer cell biochemistry. The fading of digital control in cells, however, seems not well comprehended by most. This factor, together with the loss of DNA stability that is an underpinning of cancer, virtually guarantees that chaotic dynamics are very important in cancer cells. Yet, chaos is very underappreciated in oncology. Failure to appreciate the significance of the dissolution of digital control in cell dynamics and the lack of perception of the importance of chaotic dynamics in the cancer cell are 2 errors that will tend to enhance the frequency of mistakes made in analyzing information from gene expression microarrays, proteomic microarrays, and other advances in molecular oncology. This article explains how these mistakes will come about and why, in some instances, they could result in adverse effects in patient therapy as the goals for targeted, individualized, and molecular-based treatments are sought.
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http://dx.doi.org/10.1053/j.anndiagpath.2004.10.010 | DOI Listing |
JCI Insight
January 2025
Medical Oncology Department, Research Institute for Medical Innovation, Radboud University Medical Center, Nijmegen, Netherlands.
Background: Previously, we demonstrated that changes in circulating tumor DNA (ctDNA) are promising biomarkers for early response prediction (ERP) to immune checkpoint inhibitors (ICI) in metastatic urothelial cancer (mUC). In this study, we investigated the value of whole blood immunotranscriptomics for ERP-ICI and integrated both biomarkers into a multimodal model to boost accuracy.
Methods: Blood samples of 93 patients were collected at baseline and after 2-6 weeks of ICI for ctDNA (N=88) and immunotranscriptome (N=79) analyses.
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.
View Article and Find Full Text PDFJ Am Soc Nephrol
January 2025
Selzman Institute for Kidney Health, Section of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030.
Background: Arteriovenous (AV) fistulas are the preferred access for dialysis but have a high incidence of failure. This study aims to understand the crosstalk between skeletal muscle catabolism and AV fistula maturation failure.
Methods: Skeletal muscle metabolism and AV fistula maturation were evaluated in mice with chronic kidney disease (CKD).
ACS Biomater Sci Eng
January 2025
Nano 2 Micro Material Design Lab, Department of Chemical Engineering and Technology, IIT (BHU), Varanasi 221005, India.
Herein, fluorescent calcium carbonate nanoclusters encapsulated with methotrexate (Mtx) and surface functionalized with chitosan (25 nm) (@Calmat) have been developed for the imaging and treatment of triple-negative breast cancer (TNBC). These biocompatible, pH-sensitive nanoparticles demonstrate significant potential for targeted therapy and diagnostic applications. The efficacy of nanoparticles (NPs) was evaluated in MDA-MB-231 TNBC cell lines.
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