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Thymidine Phosphorylase (dThdPase) is the rate-tissues expressed high levels of DPD (median >70 U/mg limiting enzyme that metabolizes 5'-deoxy-5-fluorouridine protein), while high concentrations of the dThdPase were (5'-dFUrd, doxifluridine), an intermediate metabolite of expressed in esophageal, cervical, breast, and pancreatic capecitabine, to the active drug 5-fluorouracil (5-FUra), while cancers and hepatoma (median >150 U/mg protein). The dihydropyrimidine dehydrogenase (DPD) catabolizes 5-FUra dThdPase/DPD ratio, which was reported to correlate with to an inactive molecule. The susceptibility of tumors to the susceptibility of human cancer xenografts to capecitabine, fluoropyrimidines is reported to correlate with tumor levels was high in esophageal, renal, breast, colorectal, and gastric of these enzymes. To obtain some insight into the tumor cancers (median ratio of > 1.5). In any of these three parameters, types susceptible to fluoropyrimidine therapy, we measured the inter-patient DPD variability for each cancer type was expression levels of these two enzymes in various types of much larger than the DPD variability among cancer types; human cancer tissues (241 tissue samples) by the ELISA highest/lowest ratios for dThdPase, DPD, and dThdPase/DPD methods. DPD exists in all the cancer types studied, such were 10-321, 7-513, and 2-293, respectively. These results as bladder, breast, cervical, colorectal, esophageal, gastric, indicate that measurements of the three parameters, DPD, hepatic, pancreatic, prostate, and renal cancers. Among them, dThdPase and dThdPase/DPD, would be useful criteria for the cervical, hepatic, pancreatic, esophageal, and breast cancer selecting cancer patients suitable for fluoropyrimidine therapy rather than for selecting cancer types.

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BackgroundExosomes or extracellular vesicles have the potential as a diagnostic marker for various diseases including cancer. In order to identify novel exosomal markers for prostate cancer (PC), we performed proteomic analysis of exosomes isolated from PC cell lines and examined the usefulness of the marker in patients.MethodsExosomes isolated by differential centrifugation from the culture medium of androgen-dependent LNCaP prostate cancer cell line and its sublines of partially androgen-independent C4, androgen-independent C4–2 and bone metastatic C4–2B were subjected to iTRAQ-based proteomic analysis. Exosomes were also isolated by immunocapture and separated by size exclusion chromatography and density gradient centrifugation. Protein expression was determined by Western blot analysis. GGT activity was measured using a fluorescent probe, γ-glutamyl hydroxymethyl rhodamine green (gGlu-HMRG). Immunohistochemical analysis of tissues was performed using anti-GGT1 antibody.ResultsAmong proteins upregulated in C4–2 and C4–2B cells than in LNCaP cells, we focused on gamma-glutamyltransferase 1 (GGT1), a cell-surface enzyme that regulates the catabolism of extracellular glutathione. The levels of both GGT1 large and small subunits were elevated in exosomes isolated from C4–2 and C4–2B cells by differential centrifugation and by immunocapture with anti-CD9 or -prostate-specific membrane antigen (PSMA) antibody. In cell lysates and exosomes, GGT1 expression correlated with GGT activity. Size exclusion chromatography of human serum demonstrated the presence of GGT activity and GGT1 subunits in fractions positive for CD9. Density gradient centrifugation revealed the co-presence of GGT1 subunits with CD9 in exosomes isolated by differential centrifugation from human serum. Since GGT activity correlated with GGT1 expression in serum exosomes isolated by differential centrifugation, we measured serum exosomal GGT activity in patients. Unexpectedly, we found that serum exosomal GGT activity was significantly higher in PC patients than in benign prostatic hyperplasia (BPH) patients. In support of this finding, immunohistochemical analysis showed increased GGT1 expression in PC tissues compared with BPH tissues.ConclusionsOur results suggest that serum exosomal GGT activity could be a useful biomarker for PC.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3301-x) contains supplementary material, which is available to authorized users.