Search

The aim of the present study was to investigate the expression of keratin 20 (KRT20) and placenta specific 8 (PLAC8) in gastrointestinal (GI) cancer with various differentiation phenotypes. The present study retrospectively investigated archived formalin-fixed paraffin-embedded tissue samples from 12 patients at different stages of GI cancer [four with gastric cancer, four with pancreatic cancer and four with colorectal cancer (CRC)]. The stages were pre-determined, according to differentiation phenotypes, by a pathologist of the Department of Pathology at Sijhih Cathay General Hospital. KRT20 and PLAC8 expression levels were assessed using immunohistochemistry. The CRC cell lines SW620 and Caco-2 were used to assess interactions between KRT20 and PLAC8 via reverse transcription-quantitative PCR. PLAC8 and KRT20 expression was observed consistently only in the well-differentiated CRC tissue samples. Low KRT20 expression levels were observed in the PLAC8 knockdown SW620 cells. In addition, there was a positive association between PLAC8 and KRT20 expression in the differentiated Caco-2 cells. According to the results of the present study, the differentiation status of GI cancer influenced KRT20 expression, particularly in CRC, which may explain why patients with well-differentiated CRC display better clinical outcomes. Therefore, the prognostic significance of KRT20 and PLAC8 may be particularly crucial for patients with CRC displaying a well-differentiated phenotype. [ABSTRACT FROM AUTHOR]

Background: The liver is the most common target organ in the metastasis of colorectal cancer (CRC). Synchronous liver metastases may confer a poorer prognosis than metachronous metastases, and genetic alterations and an inflammatory response have also been associated with a poor prognosis in cases of a liver metastasis arising from CRC. However, few studies have examined the relationship between KRAS mutations and inflammatory status in CRC, especially with respect to liver metastases. Methods: The effect of the activated mitogen-activated protein kinase pathway and another protein involved in inflammation, C-reactive protein, in liver metastases were examined. We aimed to determine the impact of the CRP-specific single nucleotide polymorphism (SNP) rs7553007 in liver metastasis on the CRC-specific survival (CSS) of patients after colorectal liver metastasectomy. Results: We found no significant differences in genotype distributions and allele frequencies at the CRP SNP rs7553007 between CRC patients with liver metastasis and the control group. CSS rates were low in the subgroup of patients with synchronous metastasis with the A-allele (A/A and A/G) at rs7553007 or mutated KRAS/BRAF in liver metastatic specimens. Furthermore, the CRP SNP rs7553007 (hazard ratio [HR] = 1.101; 95% confidence interval [CI] = 1.011–1.200; P = 0.027) and KRAS/BRAF mutations (HR = 2.377; 95% CI = 1.293–4.368; P = 0.005) remained predictive for the CSS of CRC patients with synchronous liver metastasis in multivariate analysis. Conclusions: Both the CRP SNP rs7553007 and KRAS/BRAF mutations were independent prognostic factors for CRC patients with synchronous liver metastasis. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is the predominant gastrointestinal malignancy and the leading cause of cancer death. The identification of genes related to CRC is important for the development of successful therapies and earlier diagnosis.Methods: Molecular analysis of feces was evaluated as a potential method for CRC detection. Expression of a predicted protein with unknown function, KIAA0247, was found in feces evaluated using specific quantitative real-time polymerase chain reaction. Its cellular function was then analyzed using immunofluorescent staining and the changes in the cell cycle in response to 5-fluorouracil (5-FU) were assessed.Results: Gastrointestinal tissues and peripheral blood lymphocytes ubiquitously expressed KIAA0247. 56 CRC patients fell into two group categories according to fecal KIAA0247 mRNA expression levels. The group with higher fecal KIAA0247 (n=22; ≥0.4897) had a significantly greater five-year overall survival rate than the group with lower fecal KIAA0247 (n = 30; <0.4897) (66.0 ± 11.6%; p=0.035, log-rank test). Fecal expression of KIAA0247 inversely related to CRC tumor size (Kendall's tau-b=-0.202; p=0.047). Immunofluorescent staining revealed that the cytoplasm of CRC cells evenly expresses KIAA0247 without 5-FU treatment, and KIAA0247 accumulates in the nucleus after 40 μM 5-FU treatment. In HCT116 p53(-/-) cells, which lack p53 cell cycle control, the proportion of cells in the G2/M phase was larger (13%) in KIAA0247-silent cells than in the respective shLuc control (10%) and KIAA0247-overexpressing cells (7%) after the addition of low dose (40 μM) 5-FU. Expression of three cyclin genes (cyclin A2, cyclin B1, and cyclin B2) also downregulated in the cells overexpressing KIAA0247.Conclusions: This is the first description of a linkage between KIAA0247 and CRC. The study's data demonstrate overexpression of KIAA0247 associates with 5-FU therapeutic benefits, and also identify the clinical significance of fecal KIAA0247 in CRC. [ABSTRACT FROM AUTHOR]

Background: Our previous study found that silymarin (SM) and its major pure component silibinin (SB) have anti-angiogenic effects via decreased vascular endothelium growth factor (VEGF) secretion of LoVo cells (colon cancer). We designed this consecutive study to evaluate the anti-angiogenic effects of SM/SB in vivo, and on VEGF receptor (VEGFR) gene expression. Materials and methods: We used LoVo cells exposed to SM/SB in a modified chicken chorioallantoic membrane assay (CAM) to evaluate anti-angiogenic effects. We used EA.hy 926 cells (endothelial cells) exposed to SM/SB to evaluate the effect on VEGFR-1 (Flt-1) and VEGFR-2 (KDR), with 1-step, real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Results: In CAM, SM/SB showed a dose-dependent decrease on the vascular density index (VDI) induced by LoVo cells, as did thalidomide in a concentration of 10 μg/ml. Adding escalating dosages of VEGF successfully reversed this inhibitory effect. RT-PCR revealed that SB up-regulated Flt-1 mRNA expression of EA.hy 926 cells. SM had a similar trend, although the effect was not statistically significant (P = 0.19). Neither drug effected KDR mRNA expression. Conclusion: We conclude that anti-angiogenic effects of SM/SB are associated with the up-regulation of VEGFR-1 (Flt-1) gene expression and that they are good candidates for combination therapy to treat colorectal cancer. [Copyright &y& Elsevier]