Hepatic Metabolism in Liver Health and Disease

Liu, X.; Wang, H.; Liang, Xiaowen; Roberts, Michael S.

doi:10.1016/b978-0-12-804274-8.00030-8

Cited by 27 publications

(27 citation statements)

References 43 publications

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“…In the liver, aldolase B, which is one of the three aldolase isoforms, participates in the interconversion of both fructose-1-phosphate and frutose-1,6-bisphosphate to dihydroxyacetone and glycerol-3-phosphate, which acts as a rate-limiting step for fructose metabolism in the liver (68)(69)(70)(71)(72)(73). Moreover, aldolase A and aldolase B have been linked to EMT in colon cancer, as they seem to interact with HIF-1 (74).…”

Section: Metabolism Characteristics Of Csc That Enhance Invasivenessmentioning

confidence: 99%

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

et al. 2020

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Colorectal carcinoma (CRC) is a leading cause of cancer mortality. Tumorigenesis is a dynamic process wherein cancer stem cells (CSCs) and their microenvironment promote initiation, progression, and metastasis. Metastatic colonization is an inefficient process that is very complex and is poorly understood; however, in most cases, metastatic disease is not curable, and resistance mechanisms tend to develop against conventional treatments. An understanding of the underlying mechanisms and factors that contribute to the development of metastasis in CRC can aid in the search for specific therapeutic targets for improving standard treatments. In this review, we summarize current knowledge regarding tumor biology and the use of stroma cells as prognostic factors and inflammatory inducers associated with the use of tumor microenvironments as a promoter of cancer metastasis. Moreover, we look into the importance of CSC, pericytes, and circulating tumor cells as mechanisms that lead to liver metastasis, and we also focus on the cellular and molecular pathways that modulate and regulate epithelial-mesenchymal transition. Finally, we discuss a novel therapeutic target that can potentially eliminate CSCs as a CRC treatment.

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Section: Metabolism Characteristics Of Csc That Enhance Invasivenessmentioning

confidence: 99%

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

et al. 2020

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“…Nitrogen metabolism, ammonia recycling and the urea cycle, which are fundamental processes for cellular nitrogen utilization, were found to be perturbed at both sampling time points. The liver, the main target of ethanol toxicity, is responsible for the utilization of amino acids to induce protein synthesis, pyrimidine and purine synthesis, ketogenesis, carbohydrate formation and de novo synthesis of non-essential amino acids [38].…”

Section: Discussionmentioning

confidence: 99%

Study of Fecal and Urinary Metabolite Perturbations Induced by Chronic Ethanol Treatment in Mice by UHPLC-MS/MS Targeted Profiling

et al. 2019

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Alcoholic liver disease (ALD) as a consequence of ethanol chronic consumption could lead to hepatic cirrhosis that is linked to high morbidity and mortality. Disease diagnosis is still very challenging and usually clear findings are obtained in the later stage of ALD. The profound effect of ethanol on metabolism can be depicted using metabolomics; thus, the discovery of novel biomarkers could shed light on the initiation and the progression of the ALD, serving diagnostic purposes. In the present study, Hydrophilic Interaction Liquid Chromatography tandem Mass Spectrometry HILIC-MS/MS based metabolomics analyisis of urine and fecal samples of C57BL/6 mice of both sexes at two sampling time points was performed, monitoring the effect of eight-week ethanol consumption. The altered hepatic metabolism caused by ethanol consumption induces extensive biochemical perturbations and changes in gut microbiota population on a great scale. Fecal samples were proven to be a suitable specimen for studying ALD since it was more vulnerable to the metabolic changes in comparison to urine samples. The metabolome of male mice was affected on a greater scale than the female metabolome due to ethanol exposure. Precursor small molecules of essential pathways of energy production responded to ethanol exposure. A meaningful correlation between the two studied specimens demonstrated the impact of ethanol in endogenous and symbiome metabolism.

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“…For most drugs, the clearance begins by the process of biotransformation, when portions or the entire drug undergoes chemical modification. The liver is the main but not the sole site of biotransformation, as metabolism can also occur at other sites, including the gastrointestinal mucosa, lungs and kidneys (Liu, Wang, Liang, & Roberts, 2017).…”

Section: Pharmacokinetics and Drug Efficacymentioning

confidence: 99%

Regulation Of Endocytosis By Ultrasound And Microbubble Treatment: Potential For Controlled Cellular Delivery Of Drugs To Cancer Cells

Fekri¹

2021

Preprint

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The delivery of therapeutics across biological barriers is a limiting factor in achieving ideal pharmacologic responses in patients. Modulating endocytic mechanisms with targeted, clinically-relevant interventions can increase intracellular delivery across biological barriers, and improve the efficacy of drugs. Ultrasound-microbubble (USMB) is a novel targeted delivery strategy that has shown promising potential in both diagnostic and therapeutic applications. The collective behaviour of microbubbles in the acoustic field can increase the plasma membrane permeability of surrounding cells, and enhance the delivery of therapeutics across biological barriers. USMB achieves the intracellular delivery of drugs through sonoporation and modulation of endocytic pathways, but the type of endocytic pathways and the mechanisms of activation were not known. I identified that, under distinct regulations, USMB enhances the rate of both clathrin-mediated endocytosis, as well as a non-receptor-mediated pathway responsible for internalizing bulk fluid into cells. I discovered that lysosome exocytosis and acidsphingomyelinase are required for the regulation of the clathrin-mediated pathway but not fluidphase endocytosis following USMB treatment. Given the potential of the clathrin-independent pathway to form high capacity carries for the uptake of fluids and therapeutics into cells, I aimed to identify the molecular identity of the proteins that drive the formation of non-clathrin coated vesicles following USMB treatment. I established that flotillins contribute to the USMB-induced vesicular uptake of fluid into cells, a phenomenon that depends on palmitoyltransferase DHHC5 and the Src-family kinase Fyn. Furthermore, I confirmed that USMB treatment can enhance the intracellular delivery of chemotherapeutic drugs such as cisplatin, and improve its therapeutic efficacy in a flotillin-dependent manner. This project established that both clathrin-mediated endocytosis and flotillin-dependent endocytosis can be modulated by clinically-relevant USMB treatments to enhance drug uptake and efficacy, revealing an important new strategy for targeted drug delivery in cancer treatment.

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Hepatic Metabolism in Liver Health and Disease

Cited by 27 publications

References 43 publications

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

Colorectal Cancer Stem Cells in the Progression to Liver Metastasis

Study of Fecal and Urinary Metabolite Perturbations Induced by Chronic Ethanol Treatment in Mice by UHPLC-MS/MS Targeted Profiling

Regulation Of Endocytosis By Ultrasound And Microbubble Treatment: Potential For Controlled Cellular Delivery Of Drugs To Cancer Cells

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