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      • Chemoenzymatic Synthesis of GDP-L-Fucose Derivatives as Potent and Selective -1,3-Fucosyltransferase Inhibitors

        Wei-Che Hsieh,Yu-Nong Lin,Ting-Chien Lin,Chun-Hung Hans Lin 한국당과학회 2012 한국당과학회 학술대회 Vol.2012 No.1

        Fucosyltransferases (FucTs) usually catalyze the final step of glycosylation and are critical to many biological processes. High levels of specific FucT activities are often associated with various cancers. Here we report the development of a chemoenzymatic method for synthesizing a library of GDP-L-fucose derivatives, followed by in situ screening for inhibitory activity against bacterial and human -1,3-FucTs (4). Several compounds incorporating appropriate hydrophobic moieties were identified from the initial screening. These were individually synthesized, purified and characterized in detail for their inhibition kinetics. Compound 5 had a Ki of 29 nM for human FucT-VI, and is 269 and 11 times more selective than for Helicobacter pylori FucT (Ki = 7.8 □ M) and for human FucT-V (Ki = 0.31 □ M).

      • Role of MYH Polymorphisms in Sporadic Colorectal Cancer in China: A Case-control, Population-based Study

        Yang, Liu,Huang, Xin-En,Xu, Lin,Zhou, Jian-Nong,Yu, Dong-Sheng,Zhou, Xin,Li, Dong-Zheng,Guan, Xin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.11

        Purpose: Biallelic germline variants of the 8-hydroxyguanine (8-OG) repair gene MYH have been associated with colorectal neoplasms that display somatic $G:C{\rightarrow}T:A$ transversions. However, the effect of single germline variants has not been widely studied, prompting the present investigation of monoallelic MYH variants and susceptibility to sporadic colorectal cancer (CRC) in a Chinese population. Patients and Methods: Between January 2006 and December 2012, 400 cases of sporadic CRC and 600 age- and sex-matched normal blood donors were screened randomly for 7 potentially pathogenic germline MYH exons using genetic testing technology. Variants of heterozygosity at the MYH locus were assessed in both sporadic cancer patients and healthy controls. Univariate and multivariate analyses were performed to determine risk factors for cancer onset. Results: Five monoallelic single nucleotide polymorphisms (SNPs) were identified in the 7 exon regions of MYH, which were detected in 75 (18.75%) of 400 CRC patients as well as 42 (7%) of 600 normal controls. The region of exon 1 proved to be a linked polymorphic region for the first time, a triple linked variant including exon 1-316 $G{\rightarrow}A$, exon 1-292 $G{\rightarrow}A$ and intron 1+11 $C{\rightarrow}T$, being identified in 13 CRC patients and 2 normal blood donors. A variant of base replacement, intron 10-2 $A{\rightarrow}G$, was identified in the exon 10 region in 21 cases and 7 controls, while a similar type of variant in the exon 13 region, intron 13+12 $C{\rightarrow}T$, was identified in 8 cases and 6 controls. Not the only but a newly missense variant in the present study, p. V463E (Exon 14+74 $T{\rightarrow}A$), was identified in exon 14 in 6 patients and 1 normal control. In exon 16, nt. 1678-80 del GTT with loss of heterozygosity (LOH) was identified in 27 CRC cases and 26 controls. There was no Y165C in exon 7 or G382D in exon 14, the hot-spot variants which have been reported most frequently in Caucasian studies. After univariate analysis and multivariate analysis, the linked variant in exon 1 region (p=0.002), intron 10-2 $A{\rightarrow}G$ (p=0.004) and p. V463E (p=0.036) in the MYH gene were selected as 3 independent risk factors for CRC. Conclusions: According to these results, the linked variant in Exon 1 region, Intron 10-2 $A{\rightarrow}G$ of base replacement and p. V463E of missense variant, the 3 heterozygosity variants of MYH gene in a Chinese population, may relate to the susceptibility to sporadic CRC. Lack of the hot-spot variants of Caucasians in the present study may due to the ethnic difference in MYH gene.

      • Acidic Pelvic Drainage as a Predictive Factor For Anastomotic Leakage after Surgery for Patients with Rectal Cancer

        Yang, Liu,Huang, Xin-En,Xu, Lin,Zhou, Xin,Zhou, Jian-Nong,Yu, Dong-Sheng,Li, Dong-Zheng,Guan, Xin Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.9

        Purpose: To demonstrate the value of sequential determinations of pelvic drainage in the identification of increased risk of anastomotic leakage (AL) after anterior resection for rectal cancer with a double stapling technique. Patients and Methods: Between January 2004 and December 2011, data for the daily postoperative pH of pelvic drainage fluid in 753 consecutive patients with rectal cancer who initially underwent anterior resection with a double stapling technique were reviewed. All patients experienced a total mesorectal excision. Patients with anastomotic leakage (Group AL, n=57) were compared to patients without leakage (Group nAL, n=696). Patients with perioperatively abdominopelvic implants that were likely to affect pH value (determined at $25^{\circ}C$) other than leakage were excluded. Mean postoperative values were compared. Results: Anastomotic leakage was noted in 57 (7.6%) of 753 patients with rectal cancer. The diagnosis of AL was made between the $6^{th}$ and $12^{th}$ postoperative day (POD; mean $8^{th}$ POD). There was no significance of the daily average values of pH on POD1 & 2 in group AL while a significantly sharp declining mean pH value reached its diagnostic point of AL (p<0.001) on POD3. A cut-off value of 6.978 on the $3^{rd}$ POD maximized the sensitivity (98.7.0%) and specificity (94.7%) in assessing the risk of leakage. Conclusion: According to these results, an early and persistent declining of pH value of pelvic drainage fluid after rectal surgery with anastomosis, is a marker of AL. A cut-off value of 6.798 determined at $25^{\circ}C$ on POD3 maximizes sensitivity and specificity.

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