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1.
Crit Rev Oncol Hematol ; 124: 1-10, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29548480

ABSTRACT

Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs, widely used for the treatment of a variety of cancers, both in adjuvant and in metastatic setting. Although the most common toxicities of these drugs have been extensively studied, robust data and comprehensive characterization still lack concerning fluoropyrimidine-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity. This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, uridine triacetate. The role of alternative chemotherapeutic options, namely raltitrexed and TAS-102, is discussed, and, lastly, we overview the most promising future directions in the research on FIC and development of diagnostic tools, including microRNA technology.


Subject(s)
Cardiovascular Diseases/chemically induced , Fluorouracil/adverse effects , Neoplasms/drug therapy , Pyrimidines/adverse effects , Acetates/therapeutic use , Capecitabine/therapeutic use , Cardiotoxicity/prevention & control , Cardiovascular Diseases/prevention & control , Drug Combinations , Fluorouracil/therapeutic use , Humans , Pyrimidines/therapeutic use , Pyrrolidines , Quinazolines/therapeutic use , Thiophenes/therapeutic use , Thymine , Trifluridine/therapeutic use , Uracil/analogs & derivatives , Uracil/therapeutic use , Uridine/analogs & derivatives , Uridine/therapeutic use
2.
J Neurosci ; 31(29): 10732-40, 2011 Jul 20.
Article in English | MEDLINE | ID: mdl-21775616

ABSTRACT

Auditory and written language in humans' comprehension necessitates attention to the message of interest and suppression of interference from distracting sources. Investigating the brain areas associated with the control of interference is challenging because it is inevitable that activation of the brain regions that control interference co-occurs with activation related to interference per se. To isolate the mechanisms that control verbal interference, we used a combination of structural and functional imaging techniques in Italian and German participants who spoke English as a second language. First, we searched structural MRI images of Italian participants for brain regions in which brain structure correlated with the ability to suppress interference from the unattended dominant language (Italian) while processing heard sentences in their weaker language (English). This revealed an area in the posterior paravermis of the right cerebellum in which gray matter density was higher in individuals who were better at controlling verbal interference. Second, we found functional activation in the same region when our German participants made semantic decisions on written English words in the presence of interference from unrelated words in their dominant language (German). This combination of structural and functional imaging therefore highlights the contribution of the right posterior paravermis to the control of verbal interference. We suggest that the importance of this region for language processing has previously been missed because most fMRI studies limit the field of view to increase sensitivity, with the lower part of the cerebellum being the region most likely to be excluded.


Subject(s)
Attention/physiology , Brain Mapping , Frontal Lobe/physiology , Functional Laterality/physiology , Language , Acoustic Stimulation/methods , Adult , Analysis of Variance , Comprehension/physiology , Female , Frontal Lobe/anatomy & histology , Frontal Lobe/blood supply , Frontal Lobe/diagnostic imaging , Humans , Image Processing, Computer-Assisted , Language Tests , Logistic Models , Magnetic Resonance Imaging/methods , Male , Middle Aged , Multilingualism , Neuropsychological Tests , Oxygen/blood , Photic Stimulation/methods , Positron-Emission Tomography/methods , Young Adult
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