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Colorectal Cancer
Published in Pat Price, Karol Sikora, Treatment of Cancer, 2020
Oral fluoropyrimidines. 5-FU is absorbed erratically (0–80%) and is thus not useful by this route. Capecitabine and, less commonly used, UFT (uracil and tegafur) have been developed to give sustained and predictable serum levels after oral administration. Capecitabine is an orally bioavailable pro-drug of 5-FU. Thymidine phosphorylase is required for activation, and this enzyme is also overexpressed in some CRCs, particularly in response to tumor hypoxia. Treatment with capecitabine in mCRC has been shown to be equally effective compared with 5-FU/FA.143 Myelotoxicity was found to occur with lower intensity than with 5-FU/FA, but diarrhea and palmar–plantar syndrome were experienced more frequently. On the basis of these data, capecitabine is increasingly replacing 5-FU because of greater patient convenience and reduced hospital costs.
Biology of Acinetobacter spp.
Published in E. Bergogne-Bénézin, M.L. Joly-Guillou, K.J. Towner, Acinetobacter, 2020
An important difference from many other organisms is that Acinetobacter spp. cannot incorporate extracellular thymine or thymidine into DNA because of a lack of the enzymes thymidine phosphorylase, nucleoside deoxyribosyltransferase and thymidine kinase. An additional special feature of at least one member of the genus is the ability to grow on malonate, and there has also been a report that some acinetobacters isolated from the surfaces of soybean nodules (where there may be appreciable concentrations of hydrogen because of the action of nitrogenase) can oxidise hydrogen. Further details of these and other metabolic curiosities can be found in Towner et al. (1991).
Biocatalytic Nanoreactors for Medical Purposes
Published in Peter Grunwald, Pharmaceutical Biocatalysis, 2019
Oscar González-Davis, Chauhan Kanchan, Rafael Vazquez-Duhalt
Mitochondrial neurogastrointestinal encephalomyopathy is a progressive metabolic disorder caused by thymidine phosphorylase enzyme deficiency. Clinical features include mental regression, ophthalmoplegia, and fatal gastrointestinal complications (Yadak et al., 2017). Thymidine phosphorylase was encapsulated into polymeric NPs (De Vocht et al., 2009) and erythrocytes (Moran et al., 2008) in order to prolong half-life and reduce the immunogenic reactions.
Is the benefit of using adjuvant capecitabine in patients with residual triple-negative breast cancer related to pathological response to neoadjuvant chemotherapy?
Published in Expert Review of Anticancer Therapy, 2022
Özgecan Dülgar, Başak Bala Öven, Muhammed Mustafa Atcı, Rukiye Arıkan, Seval Ay, Murat Ayhan, Oğuzhan Selvi, Deniz Tataroglu Ozyukseler, Ertuğrul Bayram, Erkan Özcan, Ayşe İrem Yasin, Mahmut Gümüş
Poor responsive group included patients with tumor with no change or minimal loss of tumor cellularity after anthracycline and taxane therapy. We can suspect chemotherapy resistance in the unresponsive group. Despite chemotherapy resistance, capecitabine improves the survival outcomes of patients in the poor response group. Capecitabine activity depends on thymidine phosphorylase enzyme expression that converts capecitabine to cytotoxic fluorouracil in tumors. Thymidine phosphorylase is highly expressed in breast cancer and up-regulated by taxanes and cyclophosphamide and by X-ray irradiation [13]. In our study, 91.1% and 88.5% of patients received adjuvant radiotherapy (RT) in poor and good response group, respectively. While the adjuvant single agent capecitabine is ineffective, post-neoadjuvant use increases the efficacy of capecitabine. In Geicam/2003-10 trial, cyclophosphamide was omitted in the experimental capecitabine arm, and the study failed to show improvement with the addition of adjuvant capecitabine despite large cohort and long follow up [14].
5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations
Published in Acta Cardiologica, 2022
Eleftherios Teperikidis, Aristi Boulmpou, Panagiotis Charalampidis, Chalil Tsavousoglou, George Giannakoulas, Christodoulos E. Papadopoulos, Vassilios Vassilikos
5-Fluorouracil (5-FU) is a chemotherapeutic agent that was first introduced in 1957. Today, it is one of the most effective and frequently used agents, either alone or as part of combination schedules, in the treatment of gastrointestinal, breast, and head and neck tumours. It is classified as a fluoropyridine antimetabolite that works by disrupting RNA synthesis directly and by inhibiting thymidylate synthetase thereby affecting DNA synthesis [1]. Similarly, capecitabine is a precursor of 5-FU, with reported preferential activation in malignant cells that is used in the treatment of metastatic colorectal and breast cancer. It is a pro-drug that follows a three step activation process within the human body. Most pertinently, the final step is catalysed by thymidine phosphorylase that has been demonstrated to be of higher activity in tumour cells [2]. Nevertheless, both agents have been reported to cause cardiotoxicity reactions at a similar rate. The first report of 5-FU cardiotoxicity was in 1969, which was followed by a large number of reports describing a large spectrum of symptoms, ranging from mild chest pain to myocardial infarction and death [3].
Efficacy of topical Lawsonia inermis L. (Henna) hydrogel in fluorouracil-induced hand-foot syndrome: a pilot randomized double-blind placebo-controlled clinical trial
Published in Cutaneous and Ocular Toxicology, 2021
Razieh Mohajerani, Farhad Shahi, Zahra Jafariazar, Minoo Afshar
One proposed remedy for this side effect is blocking the thymidine phosphorylase activity in skin24. Another strategy to protect skin from the destructive effects of free radical formation after systemic chemotherapy would be application of highly concentrated antioxidants and anti-inflammatory agents23. This was confirmed by our previous research administrating a standardized polyherbal hydrogel containing Calendula officinalis L., Matricaria recutita L. and Salvia officinalis L. with high antioxidant and anti-inflammatory activity to cancer patients, who developed symptoms of HFS while receiving fluorouracil agents. In the mentioned work, of 21 patients who completed the study, 57% and 14% showed one and two HFS grade improvements, respectively25.