Lewis blood genotypes of peptic ulcer and gastric cancer patients in Taiwan

AIM： The Lewis b （Le^b） antigen has been implicated as a possible binding site for attachment of Helicobacter pylori （H pylon） to gastric mucosa. However, studies both supporting and denying this association have been reported in the literature. Differences in secretor （Se） genotype have been suggested as a possible reason for previous discrepancies. Therefore, we investigated the relationship between Le and Se genotypes and Hpylori infection rates in people with peptic ulcer or gastric cancer. METHODS： Peripheral blood samples were obtained from 347 patients with endoscopic evidence of peptic ulcer disease （235 cases of duodenal ulcer, 62 of gastric ulcer, and 50 of combined duodenal ulcer/gastric ulcer） and 51 patients with gastric cancer on endoscopy. Peripheral blood specimens from 101 unrelated normal volunteers were used as controls. Lewis phenotype was determined using an antibody method, whereas Le and Se genotypes were determined by DNA amplification and restriction enzyme analysis. Gastric or duodenal biopsies taken from patients with endoscopic evidence of peptic ulcer or gastric cancer were cultured for Hpylotri Isolates were identified as Hpylori by morphology and production of urease and catalase. The Hpyloriinfection status was also evaluated by rapid urease test （CLO test）, and urea breath test （13^C-UBT）. Results of studies were analyzed by chi-square test （taken as significant）. RESULTS： Hpyloriwas isolated from 83.7% （303/347） of patients with peptic ulcer disease. Statistical analysis did not show any significant difference in Lewis phenotype or genotype between patients with and without Hpylori infection. No significant association was found between Lewis genotype and peptic ulcer or gastric cancer.CONCLUSION： Lewis blood genotype or phenotype may not play a role in the pathogenesis of Hpyloriinfection. However, bacterial strain differences and the presence of more than one attachment mechanism may limit the value of epidemiological studies in elucidating this matter.

Involvement of fatty acid-CoA ligase 4 in hepatocellular carcinoma growth: Roles of cyclic AMP and p38 mitogen-activated protein kinase

AIM: Fatty acid-CoA ligase 4 (FACL4) is an arachidonatepreferring enzyme which has been shown to be up-regulated in human colon cancer tissues and implicated in the colon tumorigenesis. The purpose of this study was to investigatethe role of FACL4 in the human hepatocellular carcinoma (HCC) tumorigenesis and the specific signal pathways involved in this process.METHODS: We investigated the expression and regulation of FACL4 in HCC, adjacent non-tumorous liver tissues, and cell lines.RESULTS: In HCC patients, we demonstrated that FACL4 gene expression was markedly elevated in the cancerous tissues than in the adjacent non-cancerous liver tissues.In addition, several human hepatoma cell lines, including Hep3B and HepG2, expressed high levels of FACL4. Stable overex-pression of FACL4 knockdown plasmids (small interfering RNA, siRNA) to Hep3B cells significantly decreased FACL4 expression and subsequently limited the cell proliferation. Treatment of Hep3B cells with 8bromo-cAMP and SB203508 (p38 MAPK inhibitor) significantly suppressed the FACL4 expression. CONCLUSION: FACL4 is involved in the HCC tumorigenesis and both cAMP and p38 MAPK pathways are associated with the regulation of FACL4 in HCC.

Mutation analysis of 13 driver genes of colorectalcancer-related pathways in Taiwan Residents patients

AIM To investigate the driver gene mutations associatedwith colorectal cancer （CRC） in the Taiwan Residentspopulation.METHODS： In this study, 103 patients with CRCwere evaluated. The samples consisted of 66 menand 37 women with a median age of 59 years and anage range of 26-86 years. We used high-resolutionmelting analysis （HRM） and direct DNA sequencing tocharacterize the mutations in 13 driver genes of CRCrelatedpathways. The HRM assays were conductedusing the LightCycler？ 480 Instrument provided with the software LightCycler 480 Gene Scanning SoftwareVersion 1.5. We also compared the clinicopathologicaldata of CRC patients with the driver gene mutationstatus.RESULTS： Of the 103 patients evaluated, 73.79%had mutations in one of the 13 driver genes. Wediscovered 18 novel mutations in APC , MLH1 , MSH2 ,PMS2 , SMAD4 and TP53 that have not been previouslyreported. Additionally, we found 16 de novo mutationsin APC , BMPR1A , MLH1 , MSH2 , MSH6 , MUTYH andPMS2 in cancerous tissues previously reported in thedbSNP database; however, these mutations couldnot be detected in peripheral blood cells. The APCmutation correlates with lymph node metastasis（34.69% vs 12.96%, P = 0.009） and cancer stage（34.78% vs 14.04%, P = 0.013）. No association wasobserved between other driver gene mutations andclinicopathological features. Furthermore, having twoor more driver gene mutations correlates with thedegree of lymph node metastasis （42.86% vs 24.07%,P = 0.043）.CONCLUSION： Our findings confirm the importanceof 13 CRC-related pathway driver genes in the developmentof CRC in Taiwan Residents patients.