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Abstract

Objectives: Mycophenolate mofetil is a first-line drug after organ transplant, but there are differences in metabolism of mycophenolate mofetil among individuals. The UDP glucuronosyltransferase enzyme is the key metabolic enzyme for mycophenolate mofetil, and UGT1A8 gene polymorphisms may affect the elimination of mycophenolate mofetil in patients. Here, we conducted an in vitro study to explore the relation between UGT1A8 gene polymorphisms and mycophenolate mofetil metabolism. Materials and Methods: Five mutant loci overexpression vectors (UGT1A8 128C>T, 157C>A, 431C>T, 518C>G, and 830G>A) were constructed by genetic recombination and site-directed mutagenesis. We used Lipo2000 (Invitrogen, Carlsbad, CA, USA) to transfect the vectors into HEK293 cells. Mycophenolic acid, the active ingredient of mycophenolate mofetil, was added to different groups of cells. We then used the liquid chromatography tandem-mass spectrometry technique to detect production of the metabolite 7-O-mycophenolic acid glucuronide and to evaluate activity of the UDP glucuronosyltransferase enzyme in cells with different overexpression vectors. Results: Mutations of UGT1A8 157C>A and 518C>G vectors can lead to increased activity of UDP glucuronosyltransferase enzymes and increased production of the 7-O-mycophenolic acid glucuronide metabolite, which showed 116% (P < .001) and 107% (P = .0191) production changes of 157C>A and 518C>G mutations, respectively, relative to wild-type UGT1A8. However, mutations of UGT1A8 431C>T and 830G>A loci resulted in decreased activity of UDP glucuronosyltransferase enzymes and decreased production of the metabolite, respectively showing 62.9% (P < .001) and 9.05% (P < .001) activity relative to wild-type UGT1A8. UGT1A8 128C>T had little effect on enzyme activity, with 96.8% activity relative to wild-type UGT1A8 (P = .0569). Conclusions: Our results showed that UGT1A8 gene polymorphisms can affect the activity of UDP glucuronosyltransferase enzyme, which may influence the elimination of mycophenolate mofetil in different patients.

Genome-wide DNA copy number profiling and bioinformatics analysis of ovarian cancer reveals key genes and pathways associated with distinct invasive/migratory capabilities

“…There are no reports to date regarding UGT1A8 in ovarian cancer. There is one study of recombinant human UDP-glucuronosyltransferases (UGTs), including UGT1A1, but Zhou [60] found that UGT1A8 gene polymorphisms can affect the activity of the UDP glucuronosyltransferase enzyme, which may influence the elimination of mycophenolate mofetil in different patients. The 6 CNV-driven genes identified in the present study may be potential markers for ovarian cancer.…”

<p>Comparing short-time outcomes of three-dimensional and two-dimensional totally laparoscopic surgery for colon cancer using overlapped delta-shaped anastomosis</p>

“…For overlapped delta-shaped anastomosis, disarticulation and anastomosis do not need to be performed extracorporeally; therefore, a smaller portion of the intestines is required to be freed laparoscopically. In addition, this anastomosis technique does not limit the location of the incision, so smaller Pfannenstiel incisions can be used using this technique; it is less invasive, gives better cosmetic results and can decrease the incidence of incisional hernias 13,14. Above all, this procedure is associated with fewer complaints of postoperative pain and leads to earlier postoperative recovery.…”

Intra-corporeal delta-shaped anastomosis in laparoscopic right hemicolectomy for right colon cancer: a safe and effective technique

“…The length of incision was shorter in the IDA group than in the EA group ( P < 0.001); however, we think the difference of 1 cm in length is not very significant clinically. Additionally, this technique of anastomosis does not limit the location of the incision; hence, we can apply the Pfannenstiel incision in patients in the IDA group, since it is less invasive, has better cosmesis and decreases the incidence of incisional hernia [15, 16]. Above all, it is associated with less post-operative pain.…”