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analysis
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methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE
medicine
structural insight into the binding mode of the inhibitor to this important drug target forms the basis for designing novel inhibitors for use in anticancer therapy
medicine
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thymidine phosphorylase activity might be useful in diagnostic characterization of ovarian cancer
medicine
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tumor-associated macrophages that express thymidine phosphorylase may be a good target for chermotherapy of thymidine phosphorylase positive solid tumors
medicine
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because pancreatic cancer is sensitive to 5-fluorouracil, thymidine phosphorylase-activated oral drug capecitabine in tumoral and endothelial cells and tumor infiltrating thymidine phosphorylase-positive macrophages could increase the concentration of 5-fluorouracil at tumor site, thus resulting in an enhanced antitumor activity
medicine
expression of PD-ECGF/TP may play an important role in the progression of solid tumors, and inhibitors of thymidine phosphorylase and analogs of the degradation products of thymidine may suppress the growth of tumors by promoting apoptosis
medicine
important target enzyme for cancer chemotherapy
medicine
mitochondrial neurogastrointestinal encephalomyopathy is an autosomal recessive disorder characterized by ptosis and progressive external ophthalmoplegia, peripheral neuropathy, severe gastrointestinal dysmotility, cachexia and leukoencephalopathy, morphologically abnormal mitochondria and defects of respiratory chain enzymes. Patients harbor depletion, multiple deletions, and point mutations of mitochondrial DNA. This disorder is caused by loss-offunction mutations in the gene encoding thymidine phosphorylase. In patients with mitochondrial neurogastrointestinal encephalomyopathy, thymidine phosphorylase activity is very low or absent resulting in dramatically elevated levels of plasma thymidine and deoxyuridine. It is hypothesized that the increased levels of thymidine and deoxyuridine cause mitochondrial nucleotide pool imbalances that, in turn, generate mtDNA alterations
medicine
there is no tumour-selective depletion of thymidine and there does not appear to be any potential benefit of combining antibody-targeted thymidine phosphorylase with the thymidylate synthase inhibitor raltitrexed
medicine
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thymidine phosphorylase activity in normal liver tissue adjacent to hepatocellular carcinoma is related to tumor occurrence and may predict postoperative tumor recurrence. Patients who have a high thymidine phosphorylase level in normal liver tissue have significantly earlier recurrence compared with patients who have a low thymidine phosphorylase level. Patients who have a low thymidine phosphorylase level in adjacent liver tissue have a 0.387fold higher risk of postoperative recurrence compared with patients who have a high TP level
medicine
thymidine phosphorylase expression is associated with response to capecitabine plus irinotecan in patients with metastatic colorectal cancer
medicine
thymidine phosphorylase expression seems to be an important prognostic indicator in gastric cancer patients only when the enzyme is located in tumor cells
medicine
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a high level of thymidine phosphorylase gene expression is significantly associated with favorable diagnosis of patients treated with 5-fluorouracil-based chemotherapy
medicine
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dThdPase plays an important role in tumor angiogenesis in ductal adenocarcinoma of the pancreas
medicine
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expression of thymidine phosphorylase mRNA is a useful predictive parameter for the survival of postoperative gastric cancer patients after 5-fluorouracilbased adjuvant chemotherapy
medicine
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gliostatin and vascular endothelial growth factor have synergistic effects on angiogenesis in rheumatoid synovitis
medicine
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immunhistochemical evaluation of thymidine phosphorylase expression is a promising predictor of therapeutic benefit from docetaxel-modulated capecitabine for metastatic breast cancer
medicine
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in gastric cancer, thymidine phosphorylase expression of the cancer cells, not stromal cells may play an important role in tumor growth by microvessel formation
medicine
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low tumour expression level of thymidine phosphorylase is linked with improved outcome for colorectal cancer patients treated with 5-fluorouracil, low thymidine phosphorylase protein expression is predictive of good response to 5-fluorouracil chemotherapy
medicine
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the ThdPase expression in tumors may be a predictive marker for the effectiveness in response to chemotherapy with irinotecan and 5'-deoxy-5-fluoridine
medicine
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the thymidine phosphorylase/dihydropyrimidine dehydrogenase ratio may be useful as prognostic factor in patients with pancreatic cancer
medicine
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there is no significant association between the occurrence of palmar-plantar erythrodysesthesia after capecitabine treatment and higher tumor thymidine phosphorylase levels
medicine
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thymidine phosphorylase delivers information about endometrial cancer progression
medicine
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thymidine phosphorylase enzymatic activity may be associated with lymph node metastasis
medicine
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thymidine phosphorylase expression at the invasive front of tumor may be an important prognostic factor for T3 rectal cancer
medicine
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thymidine phosphorylase expression correlates well with tumor grade, metastasis and shorter patient survival in colorectal, pancreatic, renal, ovarian, cervical, bladder and non-small cell lung cancer, loss of function mutants of thymidine phosphorylase case the disease mitochondrial neurogastrointestinal encephalomyopathy
medicine
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thymidine phosphorylase expression in breast cancer can represent a biomarker of sensitivity to capecitabine treatment
medicine
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thymidine phosphorylase expression in cancer-infiltrating inflammatory cells can affect lymph node metastasis and patients' survival in gastric cancer
medicine
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thymidine phosphorylase is a predictive biomarker in breast cancer
medicine
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thymidine phosphorylase is a predictive factor of therapeutic efficacy of capecitabine chemotherapy for breast cancer
medicine
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thymidine phosphorylase is a predictor of response to capecitabine-based chemotherapy in gastric cancer patients
medicine
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thymidine phosphorylase is an independent prognostic and therapeutic marker for nasopharyngeal carcinoma
medicine
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thymidine phosphorylase is associated with tumor angiogenesis
medicine
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thymidine phosphorylase may be involved in up-regulating P-selectin expression in breast cancer cells, tumor cell thymidine phosphorylase correlates with tumor cell P-selectin but not with endothelial cell P-selectin in vascular endothelial cells
medicine
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thymidine phosphorylase plays a role in oropharyngeal tumourigenesis and 5-fluorouracil activation in the adjuvant setting of oropharyngeal squamous cell carcinoma patients
medicine
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thymidine phosphorylase serum levels reflect the prognosis of patients with colorectal cancer, particularly the risk of liver metastasis
medicine
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thymidine phosphorylase is a promising target for the treatment of vascular obstructive diseases, effect on cancer cells, detailed overview
medicine
use of thymidine phosphorylase inhibitors might offer a promising strategy for cancer treatment
medicine
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methods to measure thymidine and deoxyuridine concentrations and thymidine phosphorylase activity in biological samples. Thymidine phosphorylase activity can be measured by an endpoint determination of the thymine formed after 1 h incubation of the buffy coat homogenate in the presence of a large excess of its substrate thymidine, either spectrophotometrically or by HPLC-UV. The protocols allow the detection of thymidine phosphorylase dysfunction in patients with mitochondrial neurogastrointestinal encephalomyopathy, MNGIE
medicine
thymidine phosphorylase is identified as a prime target for developing anticancer therapies
medicine
thymidine phosphorylase is involved regulation of intra- or extracellular thymidine concentration, angiogenesis, cancer chemotherapy, radiotherapy, as well as tumor imaging
synthesis
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construction of Escherichia coli expression vector pDEOA and use of lactose instead of IPTG to induce expression. The use of lactose at concentrations above 0.5 mmol/l has an induction effect similar to that of IPTG but results in a longer initial induction time and better cell growth. The thymidine phosphorylase induced by lactose is very stable at 50°C. Intact pDEOA cells induced by lactose can be used as a source of thymidine phosphorylase. Under standard reaction conditions, several deoxynucleosides are effectively produced from thymidine
synthesis
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immobilization of enzyme on solid support with the aim to have a stable and recyclable biocatalyst for nucleoside synthesis. Immobilization by ionic adsorption on amine-functionalized agarose and Sepabeads results in more than 85% activity recovery. Cross-linking with aldehyde dextran, MW20 kDa, decreases the percentage of expressed activity after immobilization by about 25%, but results in up to 6fold and 3fold higher stability than the soluble enzyme and the non-cross-linked counterpart, respectively, at pH 10 and 37°C. The preparation can be successfully used for the one-pot synthesis of 5-fluoro-2'-deoxyuridine starting from 2'-deoxyuridine or thymidine and 5-fluorouracil. In both cases, the reaction proceeds at the same rate leading to 62% conversion in 1 h