Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 6 de 6
Filter
Add more filters










Database
Language
Publication year range
2.
Radiol Imaging Cancer ; 5(5): e230005, 2023 09.
Article in English | MEDLINE | ID: mdl-37682052

ABSTRACT

Hyperpolarized carbon 13 MRI (13C MRI) is a novel imaging approach that can noninvasively probe tissue metabolism in both normal and pathologic tissues. The process of hyperpolarization increases the signal acquired by several orders of magnitude, allowing injected 13C-labeled molecules and their downstream metabolites to be imaged in vivo, thus providing real-time information on kinetics. To date, the most important reaction studied with hyperpolarized 13C MRI is exchange of the hyperpolarized 13C signal from injected [1-13C]pyruvate with the resident tissue lactate pool. Recent preclinical and human studies have shown the role of several biologic factors such as the lactate dehydrogenase enzyme, pyruvate transporter expression, and tissue hypoxia in generating the MRI signal from this reaction. Potential clinical applications of hyperpolarized 13C MRI in oncology include using metabolism to stratify tumors by grade, selecting therapeutic pathways based on tumor metabolic profiles, and detecting early treatment response through the imaging of shifts in metabolism that precede tumor structural changes. This review summarizes the foundations of hyperpolarized 13C MRI, presents key findings from human cancer studies, and explores the future clinical directions of the technique in oncology. Keywords: Hyperpolarized Carbon 13 MRI, Molecular Imaging, Cancer, Tissue Metabolism © RSNA, 2023.


Subject(s)
Magnetic Resonance Imaging , Medical Oncology , Humans , Carbon Isotopes , Lactic Acid
3.
Magn Reson Med ; 88(3): 1324-1332, 2022 09.
Article in English | MEDLINE | ID: mdl-35468245

ABSTRACT

PURPOSE: To determine the effect of altering anesthetic oxygen protocols on measurements of cerebral perfusion and metabolism in the rodent brain. METHODS: Seven rats were anesthetized and underwent serial MRI scans with hyperpolarized [1-13 C]pyruvate and perfusion weighted imaging. The anesthetic carrier gas protocol used varied from 100:0% to 90:10% to 60:40% O2 :N2 O. Spectra were quantified with AMARES and perfusion imaging was processed using model-free deconvolution. A 1-way ANOVA was used to compare results across groups, with pairwise t tests performed with correction for multiple comparisons. Spearman's correlation analysis was performed between O2 % and MR measurements. RESULTS: There was a significant increase in bicarbonate:total 13 C carbon and bicarbonate:13 C pyruvate when moving between 100:0 to 90:10 and 100:0 to 60:40 O2 :N2 O % (0.02 ± 0.01 vs. 0.019 ± 0.005 and 0.02 ± 0.01 vs. 0.05 ± 0.02, respectively) and (0.04 ± 0.01 vs. 0.03 ± 0.01 and 0.04 ± 0.01 vs. 0.08 ± 0.02, respectively). There was a significant difference in 13 C pyruvate time to peak when moving between 100:0 to 90:10 and 100:0 to 60:40 O2 :N2 O % (13 ± 2 vs. 10 ± 1 and 13 ± 2 vs. 7.5 ± 0.5 s, respectively) as well as significant differences in cerebral blood flow (CBF) between gas protocols. Significant correlations between bicarbonate:13 C pyruvate and gas protocol (ρ = -0.47), mean transit time and gas protocol (ρ = 0.41) and 13 C pyruvate time-to-peak and cerebral blood flow (ρ = -0.54) were also observed. CONCLUSIONS: These results demonstrate that the detection and quantification of cerebral metabolism and perfusion is dependent on the oxygen protocol used in the anesthetized rodent brain.


Subject(s)
Anesthetics, Inhalation , Bicarbonates , Anesthetics, Inhalation/pharmacology , Animals , Bicarbonates/metabolism , Brain/metabolism , Carbon Isotopes/metabolism , Magnetic Resonance Imaging/methods , Oxygen/metabolism , Pyruvic Acid/metabolism , Rats
4.
Biosci Biotechnol Biochem ; 84(12): 2448-2457, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32877316

ABSTRACT

Skeletal muscles produce secretory factors termed as myokines, which alter physiological functions of target tissues. We recently identified C-X-C chemokine ligand 10 (CXCL10) as a novel myokine, which is downregulated in response to exercise. In the present study, we investigated whether the nutritional changes affect CXCL10 expression in mouse skeletal muscle. Expression of CXCL10 was evaluated in mice fed a normal diet or a high fat diet for 10 weeks. In animals fed on HFD, Cxcl10 expression was significantly induced in fast-twitched muscles, and was accompanied by increased blood glucose and free fatty acid levels. In vitro experiments using C2C12 myotubes suggested that the increased levels of glucose and palmitic acids directly enhanced CXCL10 expression. Interestingly, the effect of palmitic acids was attenuated by palmitoleic acids. Considering its potent angiostatic activity, induction of CXCL10 by nutritional changes may contribute to the impairment of microvascular networks in skeletal muscles.


Subject(s)
Chemokine CXCL10/metabolism , Fatty Acids, Nonesterified/pharmacology , Gene Expression Regulation/drug effects , Glucose/pharmacology , Muscle, Skeletal/cytology , Animals , Dose-Response Relationship, Drug , Male , Mice , Mice, Inbred C57BL , Muscle Fibers, Skeletal/drug effects , Muscle Fibers, Skeletal/metabolism
5.
Enzyme Microb Technol ; 73-74: 65-71, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26002506

ABSTRACT

We previously described four α-l-arabinofuranosidases (ABFs) secreted by Penicillium chrysogenum 31B. Here, we cloned the fifth and sixth genes (Pcabf43B and Pcabf51C) encoding the ABFs PcABF43B and PcABF51C in this strain and overexpressed these genes in Escherichia coli. The deduced amino acid sequences of PcABF43B and PcABF51C were highly similar to putative ABFs belonging to glycoside hydrolase families 43 and 51, respectively. Semiquantitative reverse transcription polymerase chain reaction indicated that both genes were induced by arabinose, arabinitol, arabinan, and arabinoxylan; however, the Pcabf51C gene was constitutively expressed at low levels in P. chrysogenum 31B. PcABF43B had optimal activity at 20°C and pH 5-6, indicating that this enzyme was psychrophilic and had the lowest optimal temperature reported for ABFs. PcABF51C had optimal activity at 45°C and pH 6-7. Both recombinant enzymes showed high activity on arabino-oligosaccharides, but little activity on arabinose-containing polysaccharides, such as l-arabinan. Next, we compared the substrate specificities of PcABF43B, PcABF51C, and AFQ1, a P. chrysogenum ABF that preferentially degraded oligosaccharides over polysaccharides. PcABF43B was found to preferentially hydrolyze (1→3)-linkages in branched arabino-oligosaccharides and released only a small amount of arabinose from linear α-1,5-arabino-oligosaccharides. In contrast, AFQ1 and PcABF51C showed higher activities on linear arabino-oligosaccharides than on branched arabino-oligosaccharides. AFQ1 showed high catalytic efficiencies for α-1,5-l-arabinofuranobiose (α-1,5-Ara2) and α-1,5-l-arabinofuranotriose (α-1,5-Ara3) at the same level. In contrast, intracellular PcABF51C showed much higher catalytic efficiency for α-1,5-Ara2 than for α-1,5-Ara3.


Subject(s)
Fungal Proteins/isolation & purification , Genes, Fungal , Oligosaccharides/metabolism , Penicillium chrysogenum/enzymology , Amino Acid Sequence , Base Sequence , Catalysis , Cloning, Molecular , Enzyme Induction , Fungal Proteins/genetics , Fungal Proteins/metabolism , Hydrogen-Ion Concentration , Molecular Sequence Data , Penicillium chrysogenum/genetics , Polysaccharides/metabolism , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Sequence Homology , Substrate Specificity , Temperature
6.
Enzyme Microb Technol ; 58-59: 80-6, 2014 May 10.
Article in English | MEDLINE | ID: mdl-24731829

ABSTRACT

We previously described three α-l-arabinofuranosidases (ABFs) secreted by Penicillium chrysogenum 31B. Here, we purified a fourth ABF, termed PcABF43A, from the culture filtrate. The molecular mass of the enzyme was estimated to be 31kDa. PcABF43A had the highest activity at 35°C and at around pH 5. The enzyme activity was strong on sugar beet l-arabinan but weak on debranched arabinan and arabinoxylan. Low molecular-mass substrates such as p-nitrophenyl α-l-arabinofuranoside, α-1,5-l-arabinooligosaccharides, and branched arabinotriose were highly resistant to the action of PcABF43A. (1)H-NMR analysis revealed that PcABF43A hydrolyzed arabinosyl side chains linked to C-2 or C-3 of single-substituted arabinose residues in l-arabinan. Reports concerning enzymes specific for l-arabinan are quite limited. Pcabf43A cDNA encoding PcABF43A was isolated by in vitro cloning. The deduced amino acid sequence of the enzyme shows high similarities with the sequences of other fungal uncharacterized proteins. Semi-quantitative RT-PCR analysis indicated that the Pcabf43A gene was constitutively expressed in P. chrysogenum 31B at a low level, although the expression was induced with pectic components such as l-arabinose, l-rhamnose, and d-galacturonic acid. Analysis of enzymatic characteristics of PcABF43A, GH51 ABF (AFQ1), and GH54 ABF (AFS1) from P. chrysogenum suggested that PcABF43A and AFS1 function as debranching enzymes and AFQ1 plays a role of saccharification in the degradation of l-arabinan by this fungus.


Subject(s)
Fungal Proteins/isolation & purification , Glycoside Hydrolases/isolation & purification , Penicillium chrysogenum/enzymology , Polysaccharides/metabolism , Arabinose/metabolism , Culture Media , Enzyme Induction/drug effects , Escherichia coli/metabolism , Fungal Proteins/genetics , Fungal Proteins/metabolism , Genes, Fungal , Glycoside Hydrolases/genetics , Glycoside Hydrolases/metabolism , Isoenzymes/genetics , Isoenzymes/isolation & purification , Isoenzymes/metabolism , Molecular Sequence Data , Molecular Weight , Nuclear Magnetic Resonance, Biomolecular , Pectins/metabolism , Penicillium chrysogenum/genetics , Plant Extracts/metabolism , Polysaccharides/pharmacology , Recombinant Fusion Proteins/metabolism , Sequence Alignment , Sequence Homology, Nucleic Acid , Substrate Specificity
SELECTION OF CITATIONS
SEARCH DETAIL
...