Abstract：
:The increasing incidence of severe liver diseases worldwide has resulted in a high demand for curative liver transplantation. Unfortunately, the need for transplants by far eclipses the availability of suitable grafts leaving many waitlisted patients to face liver failure and often death. Routine use of smaller grafts (for example left lobes, split livers) from living or deceased donors could increase the number of life-saving transplants but is often limited by the graft versus recipient weight ratio defining the safety margins that minimize the risk of small for size syndrome (SFSS). SFSS is a severe complication characterized by failure of a small liver graft to regenerate and occurs when a donor graft is insufficient to meet the metabolic demand of the recipient, leading to liver failure as a result of insufficient liver mass. SFSS is not limited to transplantation but can also occur in the setting of hepatic surgical resections, where life-saving large resections of tumors may be limited by concerns of post-surgical liver failure. There are, as yet no available pro-regenerative therapies to enable liver regrowth and thus prevent SFSS. However, there is optimism around targeting factors and pathways that have been identified as regulators of liver regeneration to induce regrowth in vivo and ex vivo for clinical use. In this commentary, we propose a roadmap for developing such pro-regenerative therapy and for bringing it into the clinic. We summarize the clinical indications, preclinical models, pro-regenerative pathways and safety considerations necessary for developing such a drug.
journal_name
Biochem Pharmacoljournal_title
Biochemical pharmacologyauthors
Greenbaum LE,Ukomadu C,Tchorz JSdoi
10.1016/j.bcp.2020.113847subject
Has Abstractpub_date
2020-05-01 00:00:00pages
113847eissn
0006-2952issn
1873-2968pii
S0006-2952(20)30068-Xjournal_volume
175pub_type
杂志文章,评审abstract：:The effect of glutathione depletion on cytotoxicity of the anthracycline daunorubicin, and of a copper:bis-thiosemicarbazone chelate, was examined in the P388 murine leukemia and its anthracycline-resistant subline, P388/ADR. Depletion of intracellular glutathione was accomplished through exposure to buthionine sulfox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90430-2
更新日期：1986-10-01 00:00:00
abstract：:Polyamines (putrescine, spermidine and spermine) are aliphatic amines that are produced by the action of ornithine decarboxylase (ODC) in a rate-limiting and protein kinase C (PKC)-regulated step. Because high levels of polyamines are found in the synovial fluid of arthritic patients, the aim of the present study was ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2011.04.015
更新日期：2011-08-01 00:00:00
abstract：:The inhibitory effects of N-(4-hydroxyphenyl)retinamide (HPR) and its glucuronide derivative on the growth of MCF-7 human breast cancer cells in vitro were compared. The results indicate that the glucuronide had slightly greater potency and much less cytotoxicity than the free retinoid. At a concentration of 10(-6) M,...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(91)90563-k
更新日期：1991-05-15 00:00:00
abstract：:Two resistant K562 sublines have been developed by treatment with AZQ (2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone) and BZQ (2,5-bis(2-hydroxyethylamino)-3,6-diaziridinyl-1,4-benzoquinone). The ID50 values of for AZQ on K562, the AZQ-resistant sublines (AZQR) and the BZQ-resistant sublines (BZQR) were ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00155-s
更新日期：1995-08-08 00:00:00
abstract：:On the basis of previous electrophysiological studies, it has been proposed that there are three main classes of excitatory amino acid receptor in the mammalian central nervous system, which are activated preferentially by kainic acid, quisqualic acid and N-methyl-D-aspartate respectively. Although the pharmacology of...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90213-3
更新日期：1986-02-01 00:00:00
abstract：BACKGROUND/AIMS:Carnitine palmitoyl-transferase I (CPT I) catalyses the synthesis of long-chain (LC)-acylcarnitines from LC-acyl-CoA esters. It is the rate-limiting enzyme of mitochondrial fatty acid beta-oxidation (FAO) pathway and its activity is regulated by malonyl-CoA. The antiepileptic drug valproic acid (VPA) is...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2009.10.011
更新日期：2010-03-01 00:00:00
abstract：:Amodiaquine, a 4-aminoquinoline antimalarial, has been associated with hepatitis and agranulocytosis in humans. Drug hypersensitivity reactions, especially agranulocytosis, have been attributed to reactive intermediates generated by the oxidants discharged from stimulated polymorphonuclear leucocytes (PMN). The metabo...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(95)00236-s
更新日期：1995-09-28 00:00:00
abstract：:During the molecular transduction of itch, the stimulation of pruriceptors on sensory fibers leads to the activation or sensitization of ion channels, which results in a consequent depolarization of the neurons. These ion channels mostly belong to the transient receptor potential (TRP) channels, which are involved in ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2020.114310
更新日期：2021-01-01 00:00:00
abstract：:Microsomal and cytosolic epoxide hydrolase (mEH and cEH respectively) and glutathione S-transferase (GST) activities were measured in the liver, kidney, and gills of rainbow trout. Assays were optimized for time, pH, and temperature, using trans-stilbene oxide (TSO) and cis-stilbene oxide (CSO) as substrates for cEH a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90275-x
更新日期：1989-03-15 00:00:00
abstract：:The characteristics of the muscarinic receptor in isolated gastric fundic cells from rabbit were determined by radioligand binding techniques and functional tests. The dissociation constants (KDS) of selective (hexahydrosiladifenidol and pirenzepine) and non-selective (N-methylscopolamine and atropine) muscarinic rece...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(87)90209-7
更新日期：1987-09-15 00:00:00
abstract：:When INH was administered orally or intraperitoneally to pregnant female mice, the concentrations of acetyl INH and acetyl hydrazines did not vary significantly in circulating blood and in amniotic fluid. However, the concentration of INH in the amniotic fluid was significantly higher than that observed in the serum. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(83)90484-7
更新日期：1983-02-15 00:00:00
abstract：:Endomorphin-2 (Tyr-Pro-Phe-PheNH(2)) was discovered as an endogenous ligand for the mu-opioid receptor. The physiological function of endomorphin-2 as a neurotransmitter or neuromodulator may cease through the rapid enzymatic process in the synapse of brain, as for other neuropeptides. The present study was conducted ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00391-5
更新日期：2003-08-15 00:00:00
abstract：:The effects of delta 8-tetrahydrocannabinol (delta 8-THC) and its major and active metabolite, 11-hydroxy-delta 8-tetrahydrocannabinol (11-OH-delta 8-THC), on the hepatic microsomal drug-metabolizing enzyme system were studied in mice. The repeated administration of 11-OH-delta 8-THC (5 mg/kg/day, i.v.) for 3 or 7 day...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(86)90304-7
更新日期：1986-06-01 00:00:00
abstract：:A process of differentiation was observed when ob17 preadipocyte cells were stably transfected with a vector containing the cDNA of the human A1 adenosine receptor of adipose tissue. Growth of the cell lines continued but was slowed relative to untransfected cells and cells transfected with vector alone, never attaini...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(99)00069-6
更新日期：1999-07-01 00:00:00
abstract：:The dithiol-reducing thioredoxin/thioredoxin reductase system normally maintains the reduced state of key enzymes responsible for the cell's anti-oxidant defences. We therefore addressed the question of whether AW 464--a novel thioredoxin inhibitor--as well as broad spectrum dithiol ligands diamide and phenylarsine ox...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00471-4
更新日期：2003-11-01 00:00:00
abstract：:Several monoclonal antibodies against human liver glutathione S-transferase mu were developed. One of these monoclonal antibodies, called GST-3H4 was further characterized and used in this study. In hepatic tissue, after immunoblotting, GST-3H4 strains a 27 kDa protein with a pI value of 6.2. GST-3H4 recognizes other ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(90)90068-v
更新日期：1990-02-01 00:00:00
abstract：:3'-Phosphoadenosine 5'-phosphosulfate (PAPS) is the high-energy "sulfate donor" for reactions catalyzed by sulfotransferase (SULT) enzymes. The strict requirement of SULTs for PAPS suggests that PAPS synthesis might influence the rate of sulfate conjugation. In humans, PAPS is synthesized from ATP and SO(4)(2-) by two...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(03)00104-7
更新日期：2003-06-01 00:00:00
abstract：:[[trans-PtCl(NH(3))(2)](2)mu-(trans-Pt(NH(3))(2)(H(2)N(CH(2))(6)-NH(2))(2))](4+) (BBR3464) is a cationic trinuclear platinum drug that is being evaluated in phase II clinical trials for treatment of lung and ovarian cancers. The structure and DNA binding profile of BBR3464 is different from drugs commonly used clinica...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2006.12.016
更新日期：2007-05-01 00:00:00
abstract：:Activation of the pyrimidine analogue 5-fluorouracil (5-FU) to the ribonucleotide level may occur through one of the following three pathways: 1) the 5-phosphoribosyl 1-pyrophosphate (PRPP)-mediated direct transfer of ribose 5-phosphate to 5-FU as catalysed by orotate phosphoribosyltransferase; 2) the ribose 1-phospha...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(01)00650-5
更新日期：2001-07-15 00:00:00
abstract：:With the aid of a chiral derivatizing reagent and a sensitive and specific nitrogen-phosphorus gas chromatographic assay, metabolism of para-chloroamphetamine (PCA) enantiomers has been studied following incubation of racemic (RS)-, R(-)- and S(+)-PCA with rabbit liver microsomal preparations. Significant metabolism o...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(82)90228-3
更新日期：1982-01-01 00:00:00
abstract：:We have investigated the ionophoretic and apoptotic properties of the daucane sesquiterpene ferutinin and three related compounds, ferutidin, 2-alpha-hydroxyferutidin and teferin, all isolated from various species of plants from the genus Ferula. Ferutinin induced a biphasic elevation of intracellular Ca2+ in the leuk...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2004.05.016
更新日期：2004-09-01 00:00:00
abstract：:The aim of the present study was to estimate the relative contribution of rat P450 isoforms to the metabolism of caffeine and to assess the usefulness of caffeine as a marker substance for estimating the activity of P450 in rat liver and its potential for pharmacokinetic interactions in pharmacological experiments. Th...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2007.12.017
更新日期：2008-04-01 00:00:00
abstract：:In eukaryotic cells, the DNA molecule is found in the form of a nucleoprotein complex named chromatin. The basic unit of the chromatin is the nucleosome, which comprises 147 base pairs of DNA wrapped around an octamer of core histones (made of two molecules of each H2A, H2B, H3, and H4 histones). Each nucleosome is li...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/j.bcp.2006.06.016
更新日期：2006-11-30 00:00:00
abstract：:Basic fibroblast growth factor (bFGF) preserves the viability of at least 13 different cells, including epithelial, endothelial, smooth muscle and neuronal cells. In spite of this profound and rather universal effect on cell viability, detailed studies regarding the mechanism of bFGF's action have not been conducted. ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章,评审
doi：10.1016/s0006-2952(03)00486-6
更新日期：2003-10-15 00:00:00
abstract：:Most in vivo studies demonstrating decreased activities of hepatic cytochromes P450 with inflammation have used Gram-negative bacterial lipopolysaccharide (LPS) as the inflammatory stimulant. But products of Gram-positive bacteria, such as staphylococcal enterotoxin B (SEB), also stimulate inflammatory mediators, albe...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/s0006-2952(00)00250-1
更新日期：2000-05-15 00:00:00
abstract：:The azoreduction of N,N-dimethyl-4-aminoazobenzene (DAB) and N-methyl-4-amino-azobenzene (MAB) by rat liver microsomes was investigated. It was shown that measurement of azoreduction of DAB and structurally related azo dyes by the conventional method of substrate disappearance required an anaerobic environment since N...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90343-0
更新日期：1985-09-15 00:00:00
abstract：:Double-labelled [methyl-14C,5-3H]CDPcholine has been synthesized and subjected to a pharmacokinetic analysis in several biological systems. In transport experiments with intact human erythrocytes no incorporation of radioactivity is observable. On the other hand the results obtained with perfused rat liver suggest a r...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(85)90204-7
更新日期：1985-12-01 00:00:00
abstract：:Oxyntomodulin (Oxm) is a hormone which has been shown to exhibit a range of potentially beneficial actions for alleviation of obesity-diabetes. However, exploitation of Oxm-based therapies has been severely restricted due to degradation by the enzyme dipeptidylpeptidase-IV (DPP-IV). Thus, the aim of this study was to ...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/j.bcp.2010.08.010
更新日期：2010-12-01 00:00:00
abstract：:A new analogue of methotrexate was synthesized from 4-amino-4-deoxy-N10-methylpteroic acid and D,L-homocysteic acid. The product (mAPA-HCysA) was bound tightly to L1210 mouse leukemia dihydrofolate reductase (IC50 = 1 nM), inhibited L1210 cell proliferation in culture (IC50 = 0.3 microM), and prolonged the survival of...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(84)90383-6
更新日期：1984-01-01 00:00:00
abstract：:Using a continuous perfusion system, synaptosomes prepared from rat brain released [3H]norepinephrine in a Ca2+-dependent manner when pulse depolarized by briefly elevating external potassium concentrations. Tetrodotoxin (10(-7) M), a sodium channel blocker, inhibited 48% of this pulsed release, and D595 (10(-5) M), a...
journal_title：Biochemical pharmacology
pub_type： 杂志文章
doi：10.1016/0006-2952(89)90460-7
更新日期：1989-07-15 00:00:00
