Mechanism of Cell Adaptation

Fodale, Valentina; Pierobon, Mariaelena; Liotta, Lance; Petricoin, Emanuel

doi:10.1097/ppo.0b013e318212dd3d

Cited by 162 publications

(65 citation statements)

References 58 publications

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“…Most chemotherapeutic drugs work by impairing mitosis, effectively targeting fast-dividing cancer cells, however, tumor cells can develop resistance to the treatment by alteration of drug metabolism. 39 Radiation therapy works by damaging the DNA of cancerous cells through free radicals. Oxygen is a potent radio-sensitizer, increasing the effectiveness of a given dose of radiation by forming free radicals.…”

Section: Resultsmentioning

confidence: 99%

Proteomic Analysis Reveals Warburg Effect and Anomalous Metabolism of Glutamine in Pancreatic Cancer Cells

et al. 2011

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In this present work, we characterized the proteomes of pancreatic ductal adenocarcinoma (PDAC) cell line PANC-1 and normal pancreatic duct cells by mass spectrometry using LTQ-Orbitrap and identified more than 1700 proteins from each sample. On the basis of the spectra count label-free quantification approach, we identified a large number of differentially expressed metabolic enzymes and proteins involved in cytoskeleton, cell adhesion, transport, transcription, translation, and cell proliferation as well. The data demonstrated that metabolic pathways were altered in PANC-1, consistent with the Warburg effect. In addition, the comparative MS analysis unveiled anomalous metabolism of glutamine, suggesting that glutamine was largely consumed as a nitrogen donor in nucleotide and amino acid biosynthesis in PANC-1. Our analysis provides a potentially comprehensive picture of metabolism in PANC-1, which may serve as the basis of new diagnostics and treatment of PDAC.

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Section: Resultsmentioning

confidence: 99%

Proteomic Analysis Reveals Warburg Effect and Anomalous Metabolism of Glutamine in Pancreatic Cancer Cells

et al. 2011

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“…Hence, it may be said that the MDM2-P53 interaction functions as a negative feedback loop for maintaining optimal P53 level 75. Examples of the kind are too numerous to be discussed here 76. On the level of a tumor as a whole, multiple feedback loops are activated between the tumor cells and extracellular matrix, vasculature, other tumor cells and tumor microenvironment.…”

Section: Tumor As a Robust Intelligent Superorganismmentioning

confidence: 99%

Biomolecular Self-Defense and Futility of High-Specificity Therapeutic Targeting

Rosenfeld

2011

Gene�Regul Syst Bio

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Robustness has been long recognized to be a distinctive property of living entities. While a reasonably wide consensus has been achieved regarding the conceptual meaning of robustness, the biomolecular mechanisms underlying this systemic property are still open to many unresolved questions. The goal of this paper is to provide an overview of existing approaches to characterization of robustness in mathematically sound terms. The concept of robustness is discussed in various contexts including network vulnerability, nonlinear dynamic stability, and self-organization. The second goal is to discuss the implications of biological robustness for individual-target therapeutics and possible strategies for outsmarting drug resistance arising from it. Special attention is paid to the concept of swarm intelligence, a well studied mechanism of self-organization in natural, societal and artificial systems. It is hypothesized that swarm intelligence is the key to understanding the emergent property of chemoresistance.

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“…Our current understanding of drug resistance in cancer is that tumor heterogeneity and complex genetic and epigenetic changes contribute to the development of multidrug resistance (MDR). When this occurs, the cell becomes resistant to a variety of structurally and mechanistically unrelated drugs in addition to the drug initially administered (see [12, 14]).…”

Section: Introductionmentioning

confidence: 99%

The Impact of Cell Density and Mutations in a Model of Multidrug Resistance in Solid Tumors

et al. 2014

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In this paper we develop a mathematical framework for describing multidrug resistance in cancer. To reflect the complexity of the underlying interplay between cancer cells and the therapeutic agent, we assume that the resistance level is a continuous parameter. Our model is written as a system of integro-differential equations that are parametrized by the resistance level. This model incorporates the cell-density and mutation dependence. Analysis and simulations of the model demonstrate how the dynamics evolves to a selection of one or more traits corresponding to different levels of resistance. The emerging limit distribution with nonzero variance is the desirable modeling outcome as it represents tumor heterogeneity.

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Mechanism of Cell Adaptation

Cited by 162 publications

References 58 publications

Proteomic Analysis Reveals Warburg Effect and Anomalous Metabolism of Glutamine in Pancreatic Cancer Cells

Proteomic Analysis Reveals Warburg Effect and Anomalous Metabolism of Glutamine in Pancreatic Cancer Cells

Biomolecular Self-Defense and Futility of High-Specificity Therapeutic Targeting

The Impact of Cell Density and Mutations in a Model of Multidrug Resistance in Solid Tumors

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