Expression of Metallothionein in Colorectal Cancers and Synchronous Liver Metastases

Hishikawa, Yoshitaka; Kohno, Hitoshi; Ueda, Syuhei; Kimoto, Takeo; Dhar, Dipok Kumar; Kubota, Hirofumi; Tachibana, Mitsuo; Koji, Takehiko; Nagasue, Naofumi

doi:10.1159/000055368

Cited by 29 publications

(19 citation statements)

References 24 publications

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“…The analysis was performed on 9 studies reporting gender (944 patients). The following tumor types were included: bladder [44], colorectal [38], [39], [50], head and neck [41], [51], hepatocellular [25], and stomach [43]. Similarly as in the patients' age, no significance was expected.…”

Section: Resultsmentioning

confidence: 99%

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

et al. 2014

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Metallothionein (MT) has been extensively investigated as a molecular marker of various types of cancer. In spite of the fact that numerous reviews have been published in this field, no meta-analytical approach has been performed. Therefore, results of to-date immunohistochemistry-based studies were summarized using meta-analysis in this review.Web of science, PubMed, Embase and CENTRAL databases were searched (up to April 30, 2013) and the eligibility of individual studies and heterogeneity among the studies was assessed. Random and fixed effects model meta-analysis was employed depending on the heterogeneity, and publication bias was evaluated using funnel plots and Egger's tests.A total of 77 studies were included with 8,015 tissue samples (4,631 cases and 3,384 controls). A significantly positive association between MT staining and tumors (vs. healthy tissues) was observed in head and neck (odds ratio, OR 9.95; 95% CI 5.82–17.03) and ovarian tumors (OR 7.83; 1.09–56.29), and a negative association was ascertained in liver tumors (OR 0.10; 0.03–0.30). No significant associations were identified in breast, colorectal, prostate, thyroid, stomach, bladder, kidney, gallbladder, and uterine cancers and in melanoma. While no associations were identified between MT and tumor staging, a positive association was identified with the tumor grade (OR 1.58; 1.08–2.30). In particular, strong associations were observed in breast, ovarian, uterine and prostate cancers. Borderline significant association of metastatic status and MT staining were determined (OR 1.59; 1.03–2.46), particularly in esophageal cancer. Additionally, a significant association between the patient prognosis and MT staining was also demonstrated (hazard ratio 2.04; 1.47–2.81). However, a high degree of inconsistence was observed in several tumor types, including colorectal, kidney and prostate cancer.Despite the ambiguity in some tumor types, conclusive results are provided in the tumors of head and neck, ovary and liver and in relation to the tumor grade and patient survival.

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Section: Resultsmentioning

confidence: 99%

Metallothionein – Immunohistochemical Cancer Biomarker: A Meta-Analysis

et al. 2014

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“…In human colon cancer cells metallothionein was found to be a possible proliferation marker, as it is higher expressed in proliferating cells and its expression is cell cycle regulated [45]. Expression of metallothionein in colon tumors is associated with poor prognosis [46]. …”

Section: Resultsmentioning

confidence: 99%

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et al. 2004

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BackgroundCurcumin is a spice and a coloring food compound with a promising role in colon cancer prevention. Curcumin protects against development of colon tumors in rats treated with a colon carcinogen, in colon cancer cells curcumin can inhibit cell proliferation and induce apoptosis, it is an anti-oxidant and it can act as an anti-inflammatory agent. The aim of this study was to elucidate mechanisms and effect of curcumin in colon cancer cells using gene expression profiling.MethodsGene expression changes in response to curcumin exposure were studied in two human colon cancer cell lines, using cDNA microarrays with four thousand human genes. HT29 cells were exposed to two different concentrations of curcumin and gene expression changes were followed in time (3, 6, 12, 24 and 48 hours). Gene expression changes after short-term exposure (3 or 6 hours) to curcumin were also studied in a second cell type, Caco-2 cells.ResultsGene expression changes (>1.5-fold) were found at all time points. HT29 cells were more sensitive to curcumin than Caco-2 cells. Early response genes were involved in cell cycle, signal transduction, DNA repair, gene transcription, cell adhesion and xenobiotic metabolism. In HT29 cells curcumin modulated a number of cell cycle genes of which several have a role in transition through the G2/M phase. This corresponded to a cell cycle arrest in the G2/M phase as was observed by flow cytometry. Functional groups with a similar expression profile included genes involved in phase-II metabolism that were induced by curcumin after 12 and 24 hours. Expression of some cytochrome P450 genes was downregulated by curcumin in HT29 and Caco-2 cells. In addition, curcumin affected expression of metallothionein genes, tubulin genes, p53 and other genes involved in colon carcinogenesis.ConclusionsThis study has extended knowledge on pathways or processes already reported to be affected by curcumin (cell cycle arrest, phase-II genes). Moreover, potential new leads to genes and pathways that could play a role in colon cancer prevention by curcumin were identified.

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“…However, its association with patient prognosis is far from clear, with most reports showing a lack of correlation between MT and OS and DFS [17][18][19][20]. Ofner et al [21], however, report a statistically significant association of these variables with lower MT levels, whereas another study associated higher MT expression with worse prognosis, although the number of cases was low [22].…”

Section: Discussionmentioning

confidence: 99%