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Your search keyword '"Zhao, Hai-Lu"' showing total 28 results
Start Over Author "Zhao, Hai-Lu" Publisher elsevier bv
28 results on '"Zhao, Hai-Lu"'

7. Pharmacological Inhibition of Nicotinamide Phosphoribosyltransferase (NAMPT), an Enzyme Essential for NAD+ Biosynthesis, in Human Cancer Cells

Author

Kenneth D. Roth, Saravanan Parthasarathy, Tao Wang, Robert L. Shepard, Burkholder Timothy P, Zhao Hai Lu, Gillig James Ronald, Timothy I. Meier, Karen L. Huss, Ming-Shang Kuo, Bo Tan, Genshi Zhao, Yan Zhai, Michele C. Smith, Sandaruwan Geeganage, and Debra A. Young

Subjects
Nicotinamide phosphoribosyltransferase, Dehydrogenase, Cell Biology, Pentose phosphate pathway, Biology, Biochemistry, Citric acid cycle, chemistry.chemical_compound, Metabolic pathway, chemistry, Glyceraldehyde, Glycolysis, NAD+ kinase, Molecular Biology
Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first rate-limiting step in converting nicotinamide to NAD+, essential for cellular metabolism, energy production, and DNA repair. NAMPT has been extensively studied because of its critical role in these cellular processes and the prospect of developing therapeutics against the target, yet how it regulates cellular metabolism is not fully understood. In this study we utilized liquid chromatography-mass spectrometry to examine the effects of FK866, a small molecule inhibitor of NAMPT currently in clinical trials, on glycolysis, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and serine biosynthesis in cancer cells and tumor xenografts. We show for the first time that NAMPT inhibition leads to the attenuation of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step due to the reduced availability of NAD+ for the enzyme. The attenuation of glycolysis results in the accumulation of glycolytic intermediates before and at the glyceraldehyde 3-phosphate dehydrogenase step, promoting carbon overflow into the pentose phosphate pathway as evidenced by the increased intermediate levels. The attenuation of glycolysis also causes decreased glycolytic intermediates after the glyceraldehyde 3-phosphate dehydrogenase step, thereby reducing carbon flow into serine biosynthesis and the TCA cycle. Labeling studies establish that the carbon overflow into the pentose phosphate pathway is mainly through its non-oxidative branch. Together, these studies establish the blockade of glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step as the central metabolic basis of NAMPT inhibition responsible for ATP depletion, metabolic perturbation, and subsequent tumor growth inhibition. These studies also suggest that altered metabolite levels in tumors can be used as robust pharmacodynamic markers for evaluating NAMPT inhibitors in the clinic. Background: NAMPT catalyzes the rate-limiting reaction in converting nicotinamide to NAD+ in cancers. Results: NAMPT inhibition attenuates glycolysis at the glyceraldehyde 3-phosphate dehydrogenase step, resulting in perturbing metabolic pathways related to glycolysis. Conclusion: The metabolic basis of NAMPT inhibition is the attenuation of glycolysis by reducing NAD+ available to glyceraldehyde 3-phosphate dehydrogenase. Significance: This study sheds new light on how NAMPT regulates cancer metabolism.

Published
2013
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8. P1.04-07 Pemetrexed Enhances Anti-Tumor Efficacy of PD-L1 blockade by Promoting Intra-Tumor Immune Response via Tumor and T Cell-Intrinsic Mechanisms

Author

Gerald Hall, David Schaer, Nelusha Amaladas, Bonita D. Jones, Bo Tan, Frank C. Dorsey, Kenneth D. Roth, Thompson N. Doman, Gregory P. Donoho, Andrew Capen, Ruslan D. Novosiadly, Alexander Nikolayev, Manisha Brahmachary, Zhao Hai Lu, Andreas Sonyi, Michael Kalos, Carmine Carpenito, Darin Chin, Sandaruwan Geeganage, Catalina Meyer, Jason Manro, Erik R. Rasmussen, Yiwen Li, Krishna Chodavarapu, Shuang Luo, and Xiaodong Huang

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Antitumor activity, biology, business.industry, T cell, Blockade, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Immune system, medicine.anatomical_structure, Pemetrexed, Oncology, 030220 oncology & carcinogenesis, PD-L1, biology.protein, Cancer research, medicine, business, medicine.drug
Published
2018
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12. P3.07-006 Pemetrexed Exerts Intratumor Immunomodulatory Effects and Enhances Efficacy of Immune Checkpoint Blockade in MC38 Syngeneic Mouse Tumor Model

Author

Shuang Luo, Sandaruwan Geeganage, Nelusha Amaladas, Gregory P. Donoho, Zhao Hai Lu, Ruslan D. Novosiadly, Jason Manro, Michael Kalos, Andrew Capen, Catalina Meyer, Thompson N. Doman, David Schaer, Gerald Hall, and T. Smeal

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, business.industry, Pharmacology, Immune checkpoint, Blockade, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Pemetrexed, Oncology, 030220 oncology & carcinogenesis, Medicine, Syngeneic mouse, business, medicine.drug
Published
2017
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14. CXCR4 Sequences Involved in Coreceptor Determination of Human Immunodeficiency Virus Type-1 Tropism

Author

Matthew Sharron, Zhao-hai Lu, Yin-Hua Cen, Zi-xuan Wang, Yi Sun, Joanne F. Berson, Tian-yuan Zhang, and Stephen C. Peiper

Subjects
chemistry.chemical_classification, Mutation, viruses, virus diseases, Lipid bilayer fusion, Mutagenesis (molecular biology technique), Cell Biology, Alanine scanning, Biology, medicine.disease_cause, Biochemistry, Virology, Chemokine receptor, chemistry, Coreceptor activity, medicine, Glycoprotein, Molecular Biology, Tropism
Abstract

The interaction of human immunodeficiency virus type 1 (HIV-1) with CD4 and one of a cadre of chemokine receptors triggers conformational changes in the HIV-1 envelope (Env) glycoprotein that lead to membrane fusion. The coreceptor activity of the second extracellular loop of CXCR4, which is restricted to dual tropic and T-tropic strains, was insensitive to the removal of charged residues either singly or in combinations by alanine scanning mutagenesis or to the conversion of acidic residues to lysine. Conversion of Asp-187 to a neutral residue exclusively unmasked activity with M-tropic Env in fusion and infection experiments. Insertion of the D187V mutation into chimeras containing extracellular loop 2 of CXCR4 in a CXCR2 framework also resulted in the acquisition of M-tropic coreceptor activity. The independence of CXCR4 coreceptor activity from charged residues and the extension of its repertoire by removing Asp-187 suggest that this interaction is not electrostatic and that coreceptors have the potential to be utilized by a spectrum of Env, which may be masked by charged amino acids in extracellular domains. These findings indicate that the primary structural determinants of coreceptors that program reactivity with M-, dual, and T-tropic Env are surprisingly subtle and that relatively insignificant changes in CXCR4 can dramatically alter utilization by Env of varying tropism.

Published
1998
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18. Renal Carcinogenesis After Uninephrectomy

Author

Sui, Yi, primary, Zhao, Hai-Lu, additional, Man Lee, Heung, additional, Guan, Jing, additional, He, Lan, additional, Lai, Fernand M.M., additional, Tong, Peter C.Y., additional, and Chan, Juliana C.N., additional

Published
2009
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19. Phycocyanin protects INS-1E pancreatic beta cells against human islet amyloid polypeptide-induced apoptosis through attenuating oxidative stress and modulating JNK and p38 mitogen-activated protein kinase pathways

Author

Li, Xiao-Ling, primary, Xu, Gang, additional, Chen, Tianfeng, additional, Wong, Yum-Shing, additional, Zhao, Hai-Lu, additional, Fan, Rong-Rong, additional, Gu, Xue-Mei, additional, Tong, Peter C.Y., additional, and Chan, Juliana C.N., additional

Published
2009
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22. Fat redistribution and adipocyte transformation in uninephrectomized rats

Author

Zhao, Hai-Lu, primary, Sui, Yi, additional, Guan, Jing, additional, He, Lan, additional, Zhu, Xun, additional, Fan, Rong-Rong, additional, Xu, Gang, additional, Kong, Alice P.S., additional, Ho, Chung Shun, additional, Lai, Fernand M.M., additional, Rowlands, Dewi K., additional, Chan, Juliana C.N., additional, and Tong, Peter C.Y., additional

Published
2008
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