The Experts below are selected from a list of 255 Experts worldwide ranked by ideXlab platform
J F Geschwind - One of the best experts on this subject based on the ideXlab platform.
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tumor Glycolysis as a target for cancer therapy progress and prospects
Molecular Cancer, 2013Co-Authors: Shanmugasundaram Ganapathykanniappan, J F GeschwindAbstract:Altered energy metabolism is a biochemical fingerprint of cancer cells that represents one of the “hallmarks of cancer”. This metabolic phenotype is characterized by preferential dependence on Glycolysis (the process of conversion of glucose into pyruvate followed by lactate production) for energy production in an oxygen-independent manner. Although Glycolysis is less efficient than oxidative phosphorylation in the net yield of adenosine triphosphate (ATP), cancer cells adapt to this mathematical disadvantage by increased glucose up-take, which in turn facilitates a higher rate of Glycolysis. Apart from providing cellular energy, the metabolic intermediates of Glycolysis also play a pivotal role in macromolecular biosynthesis, thus conferring selective advantage to cancer cells under diminished nutrient supply. Accumulating data also indicate that intracellular ATP is a critical determinant of chemoresistance. Under hypoxic conditions where Glycolysis remains the predominant energy producing pathway sensitizing cancer cells would require intracellular depletion of ATP by inhibition of Glycolysis. Together, the oncogenic regulation of Glycolysis and multifaceted roles of glycolytic components underscore the biological significance of tumor Glycolysis. Thus targeting Glycolysis remains attractive for therapeutic intervention. Several preclinical investigations have indeed demonstrated the effectiveness of this therapeutic approach thereby supporting its scientific rationale. Recent reviews have provided a wealth of information on the biochemical targets of Glycolysis and their inhibitors. The objective of this review is to present the most recent research on the cancer-specific role of glycolytic enzymes including their non-glycolytic functions in order to explore the potential for therapeutic opportunities. Further, we discuss the translational potential of emerging drug candidates in light of technical advances in treatment modalities such as image-guided targeted delivery of cancer therapeutics.
Karen H Vousden - One of the best experts on this subject based on the ideXlab platform.
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serine starvation induces stress and p53 dependent metabolic remodelling in cancer cells
Nature, 2013Co-Authors: Oliver D K Maddocks, Celia R Berkers, Susan Mason, Liang Zheng, Karen Blyth, Eyal Gottlieb, Karen H VousdenAbstract:Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including Glycolysis1, 2, oxidative phosphorylation3, glutaminolysis4, 5 and anti-oxidant response6. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress7, a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p538. Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic Glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours.
Oliver D K Maddocks - One of the best experts on this subject based on the ideXlab platform.
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serine starvation induces stress and p53 dependent metabolic remodelling in cancer cells
Nature, 2013Co-Authors: Oliver D K Maddocks, Celia R Berkers, Susan Mason, Liang Zheng, Karen Blyth, Eyal Gottlieb, Karen H VousdenAbstract:Cancer cells acquire distinct metabolic adaptations to survive stress associated with tumour growth and to satisfy the anabolic demands of proliferation. The tumour suppressor protein p53 (also known as TP53) influences a range of cellular metabolic processes, including Glycolysis1, 2, oxidative phosphorylation3, glutaminolysis4, 5 and anti-oxidant response6. In contrast to its role in promoting apoptosis during DNA-damaging stress, p53 can promote cell survival during metabolic stress7, a function that may contribute not only to tumour suppression but also to non-cancer-associated functions of p538. Here we show that human cancer cells rapidly use exogenous serine and that serine deprivation triggered activation of the serine synthesis pathway and rapidly suppressed aerobic Glycolysis, resulting in an increased flux to the tricarboxylic acid cycle. Transient p53-p21 (also known as CDKN1A) activation and cell-cycle arrest promoted cell survival by efficiently channelling depleted serine stores to glutathione synthesis, thus preserving cellular anti-oxidant capacity. Cells lacking p53 failed to complete the response to serine depletion, resulting in oxidative stress, reduced viability and severely impaired proliferation. The role of p53 in supporting cancer cell proliferation under serine starvation was translated to an in vivo model, indicating that serine depletion has a potential role in the treatment of p53-deficient tumours.
B.Z. Wan - One of the best experts on this subject based on the ideXlab platform.
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Investigation of catalytic Glycolysis of polyethylene terephthalate by differential scanning calorimetry
Thermochimica Acta, 1997Co-Authors: C Y Kao, W.h. Cheng, B.Z. WanAbstract:The Glycolysis of polyethylene terephthalate resin with excess amount of ethylene glycol, using metal acetates as catalysts, was examined by differential scanning calorimetry (DSC). The experiments were carried out under a nitrogen atmosphere of 600 psi. The efficiency of Glycolysis was measured from the peak temperature associated with reaction endotherm. Among all the catalysts studied zinc acetate was confirmed to be the most effective for Glycolysis. The glycolyzed products were mainly composed of small oligomers of bis-hydroxyethyl terephthalate in the presence of zinc acetate. Two isoconversion methods of kinetic analysis were applied for estimating the activation energy of Glycolysis. The activation energy was lowered either by adding zinc acetate or by decreasing resin size. The results suggest that the depolymerization or the removal of polymer molecules from solid matrix should be the rate-limiting step of polyethylene terephthalate (PET) Glycolysis, and that zinc acetate might facilitate the bond scission of polymer chains.
Alessandro Carugo - One of the best experts on this subject based on the ideXlab platform.
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increased tumor Glycolysis characterizes immune resistance to adoptive t cell therapy
Cell Metabolism, 2018Co-Authors: Tina Cascone, Jodi A Mckenzie, Rina M Mbofung, Simone Punt, Zhe Wang, Chunyu Xu, Leila Williams, Zhiqiang Wang, Christopher A Bristow, Alessandro CarugoAbstract:Summary Adoptive T cell therapy (ACT) produces durable responses in some cancer patients; however, most tumors are refractory to ACT and the molecular mechanisms underlying resistance are unclear. Using two independent approaches, we identified tumor Glycolysis as a pathway associated with immune resistance in melanoma. Glycolysis-related genes were upregulated in melanoma and lung cancer patient samples poorly infiltrated by T cells. Overexpression of Glycolysis-related molecules impaired T cell killing of tumor cells, whereas inhibition of Glycolysis enhanced T cell-mediated antitumor immunity in vitro and in vivo . Moreover, Glycolysis-related gene expression was higher in melanoma tissues from ACT-refractory patients, and tumor cells derived from these patients exhibited higher glycolytic activity. We identified reduced levels of IRF1 and CXCL10 immunostimulatory molecules in highly glycolytic melanoma cells. Our findings demonstrate that tumor Glycolysis is associated with the efficacy of ACT and identify the Glycolysis pathway as a candidate target for combinatorial therapeutic intervention.
