104 research outputs found
The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases
Get PDFSelected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.Fil: Marullo, Rossella. Cornell University; Estados UnidosFil: Castro, Monica. Universidad de Buenos Aires; ArgentinaFil: Yomtoubian, Shira. Cornell University; Estados UnidosFil: Nieves Calvo Vidal, M.. Cornell University; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krumsiek, Jan. Cornell University; Estados UnidosFil: Nicholas, Andrew P.. Cornell University; Estados UnidosFil: Cresta Morgado, Pablo. Universidad de Buenos Aires; ArgentinaFil: Yang, ShaoNing. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Roth, Berta María Cristina. Universidad de Buenos Aires; ArgentinaFil: Bonomi, Marcelo. Ohio State University; Estados UnidosFil: Keshari, Kayvan R.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Mittal, Vivek. Cornell University; Estados UnidosFil: Navigante, Alfredo Hugo. Universidad de Buenos Aires; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin
Cancer Metabolism and Tumor Heterogeneity: Imaging Perspectives Using MR Imaging and Spectroscopy
Get PDFCancer cells reprogram their metabolism to maintain viability via genetic mutations and epigenetic alterations, expressing overall dynamic heterogeneity. The complex relaxation mechanisms of nuclear spins provide unique and convertible tissue contrasts, making magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) pertinent imaging tools in both clinics and research. In this review, we summarized MR methods that visualize tumor characteristics and its metabolic phenotypes on an anatomical, microvascular, microstructural, microenvironmental, and metabolomics scale. The review will progress from the utilities of basic spin-relaxation contrasts in cancer imaging to more advanced imaging methods that measure tumor-distinctive parameters such as perfusion, water diffusion, magnetic susceptibility, oxygenation, acidosis, redox state, and cell death. Analytical methods to assess tumor heterogeneity are also reviewed in brief. Although the clinical utility of tumor heterogeneity from imaging is debatable, the quantification of tumor heterogeneity using functional and metabolic MR images with development of robust analytical methods and improved MR methods may offer more critical roles of tumor heterogeneity data in clinics. MRI/MRS can also provide insightful information on pharmacometabolomics, biomarker discovery, disease diagnosis and prognosis, and treatment response. With these future directions in mind, we anticipate the widespread utilization of these MR-based techniques in studying in vivo cancer biology to better address significant clinical needs.</jats:p
Chemistry and biochemistry of 13 C hyperpolarized magnetic resonance using dynamic nuclear polarization
No full textChemistry and biochemistry of 13 C hyperpolarized magnetic resonance using dynamic nuclear polarization
Get PDFThe study of transient chemical phenomena by conventional NMR has proved elusive, particularly for non-(1)H nuclei. For (13)C, hyperpolarization using the dynamic nuclear polarization (DNP) technique has emerged as a powerful means to improve SNR. The recent development of rapid dissolution DNP methods has facilitated previously impossible in vitro and in vivo study of small molecules. This review presents the basics of the DNP technique, identification of appropriate DNP substrates, and approaches to increase hyperpolarized signal lifetimes. Also addressed are the biochemical events to which DNP-NMR has been applied, with descriptions of several probes that have met with in vivo success
Generating contrast in hyperpolarized 13C MRI using ligand–receptor interactions
Get PDFWe report the imaging of β-cyclodextrin/benzoic acid binding at 14T using hyperpolarized 13C magnetic resonance (MR). Benzoic acid was polarized using a dynamic nuclear polarization (DNP) approach and combined with β-cyclodextrin in aqueous solution. As anticipated, decreases in the spin-lattice relaxation constant (T1) were observed with decreases in the ligand/ receptor ratio. The calculated log K was approximately 1.7, similar to previously reported binding constants. Hyperpolarized [1-13C] benzoic acid was used to interrogate solutions of variable β-cyclodextrin concentration, with the mixtures imaged at 14T using a 3D frequency-selective MR sequence. Differences in β-cyclodextrin concentration were easily visualized. These results suggest that hyperpolarized 13C MR could be used in vivo to determine the presence, and density of receptors for a given ligand-receptor pair
The Potential of Metabolic Imaging
Get PDFMetabolic imaging is a field of molecular imaging that focuses and targets changes in metabolic pathways for the evaluation of different clinical conditions. Targeting and quantifying metabolic changes noninvasively is a powerful approach to facilitate diagnosis and evaluate therapeutic response. This review addresses only techniques targeting metabolic pathways. Other molecular imaging strategies, such as affinity or receptor imaging or microenvironment-dependent methods are beyond the scope of this review. Here we describe the current state of the art in clinically translatable metabolic imaging modalities. Specifically, we focus on PET and MR spectroscopy, including conventional (1)H- and (13)C-MR spectroscopy at thermal equilibrium and hyperpolarized MRI. In this article, we first provide an overview of metabolic pathways that are altered in many pathologic conditions and the corresponding probes and techniques used to study those alterations. We then describe the application of metabolic imaging to several common diseases, including cancer, neurodegeneration, cardiac ischemia, and infection or inflammation
Factors associating with or predicting more cited or higher quality journal articles: An Annual Review of Information Science and Technology (ARIST) paper
Get PDF© 2023 The Authors. Published by Wiley. This is an open access article available under a Creative Commons licence.
The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1002/asi.24810Identifying factors that associate with more cited or higher quality research may be useful to improve science or to support research evaluation. This article reviews evidence for the existence of such factors in article text and metadata. It also reviews studies attempting to estimate article quality or predict long term citation counts using statistical regression or machine learning for journal articles or conference papers. Although the primary focus is on document-level evidence, the related task of estimating the average quality scores of entire departments from bibliometric information is also considered. The review lists a huge range of factors that associate with higher quality or more cited research in some contexts (fields, years, journals) but the strength and direction of association often depends on the set of papers examined, with little systematic pattern and rarely any cause-and-effect evidence. The strongest patterns found include the near universal usefulness of journal citation rates, author numbers, reference properties, and international collaboration in predicting (or associating with) higher citation counts, and the greater usefulness of citation-related information for predicting article quality in the medical, health and physical sciences than in engineering, social sciences, arts, and humanities
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