Number Of Colorectal Tumors Research Articles

The Effects of the Food Additive Titanium Dioxide (E171) on Tumor Formation and Gene Expression in the Colon of a Transgenic Mouse Model for Colorectal Cancer.

Titanium dioxide (TiO2) is present in many different food products as the food additive E171, which is currently scrutinized due to its potential adverse effects, including the stimulation of tumor formation in the gastrointestinal tract. We developed a transgenic mouse model to examine the effects of E171 on colorectal cancer (CRC), using the Cre-LoxP system to create an Apc-gene-knockout model which spontaneously develops colorectal tumors. A pilot study showed that E171 exposed mice developed colorectal adenocarcinomas, which were accompanied by enhanced hyperplasia in epithelial cells, lymphatic nodules at the base of the polyps, and increased tumor size. In the main study, tumor formation was studied following the exposure to 5 mg/kgbw/day of E171 for 9 weeks (Phase I). E171 exposure showed a statistically nonsignificant increase in the number of colorectal tumors in these transgenic mice, as well as a statistically nonsignificant increase in the average number of mice with tumors. Gene expression changes in the colon were analyzed after exposure to 1, 2, and 5 mg/kgbw/day of E171 for 2, 7, 14, and 21 days (Phase II). Whole-genome mRNA analysis revealed the modulation of genes in pathways involved in the regulation of gene expression, cell cycle, post-translational modification, nuclear receptor signaling, and circadian rhythm. The processes associated with these genes might be involved in the enhanced tumor formation and suggest that E171 may contribute to tumor formation and progression by modulation of events related to inflammation, activation of immune responses, cell cycle, and cancer signaling.

Effect and mechanism of EGFR expression in macrophages on the anti-cancer effect of berberine on colorectal cancer

To investigate the effect and explore its possible mechanisms of epidermal growth factor receptor(EGFR) expression in macrophages on the anti-cancer effect of berberine (BER) on the growth of colorectal cancer. Mice with EGFR gene defects in macrophages (Egfr(fl/fl) LysM-Cre) and with EGFR gene expression in macrophages (LysM-Cre) (control group) were treated with azoxymethane (AOM) to establish colorectal tumor models. These models were treated with or without berberine (BER) intervention. The number of colorectal tumors and the gut length in the two groups were measured. The proliferation of tumor cells was detected by Ki-67 immunohistochemistry and apoptosis was detected by annexin V-FITC fluorescence labeling. Western blot was used to detect the expression of cleaved-caspase-3 protein. After treated with AOM, the colorectal tumor number was 10.26 ± 1.43 in the LysM-Cre group and 7.62 ± 1.05 in the Egfr(fl/fl) LysM-Cre group, showing a significant difference (P = 0.021). The gut length was (6.04 ± 1.06) cm in the LysM-Cre group and (6.39 ± 0.92) cm in the gfrfl/flLysM-Cre group, with a non-significant difference between the two groups (P = 0.075). After treated with AOM plus BER intervention, the colorectal tumor number of the LysM-Cre group was 8.35 ± 1.22 and that in the Egfr(fl/fl) LysM-Cre group was 2.66 ± 0.38, showing a very significant difference between the two groups (P = 0.006). The gut length of the LysM-Cre group was (7.34 ± 1.16) cm and that of the Egfr(fl/fl) LysM-Cre group was (10.01 ± 1.72) cm (P = 0.028). After treated with AOM, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (78.31 ± 3.43)% and that in the Egfr(fl/fl) LysM-Cre group was (75.85 ± 2.92)% (P = 0.282). After AOM plus BER treatment, the ratio of Ki-67-positive tumor cells in the LysM-Cre group was (42.43 ± 3.09)% and that in the Egfr(fl/fl) LysM-Cre group was significantly lower (29.65 ± 2.47)% (P = 0.018). The ratio of annexin V-positive tumor cells was (0.95 ± 0.13)% in the LysM-Cre group, not significantly different from (1.13 ± 0.16)% in the Egfr(fl/fl) LysM-Cre group (P = 0.175). After AOM plus BER treatment, the ratio of annexin V-positive tumor cells in the LysM-Cre group was (32.10 ± 1.97)%, significantly lower than the (47.08 ± 2.83)% in the Egfr(fl/fl) LysM-Cre group (P = 0.010). The level of cleaved-caspase-3 protein expression was 235.92 ± 19.73 in the Egfr(fl/fl) LysM-Cre group, significantly higher than the 119.71 ± 12.87 in the LysM-Cre group (P = 0.012). The growth of colorectal cancer cells in mice can be inhibited by BER treatment, and this anti-cancer effect of BER can be further enhanced by EGFR gene knockout in macrophages. The mechanisms may be related to the inhibition of proliferation and promotion of apoptosis in colorectal cancer cells.

The cables gene on chromosome 18Q regulates colon cancer progression in vivo

Early events involved in the pathogenesis of colorectal cancer include mutations in the Adenomatous Polyposis Coli tumor-suppressor gene and oncogenic KRAS mutations. Later events include deletions on chromosome 18q, which are observed in a high proportion of colorectal cancers. However, the important tumor suppressor genes targeted by these deletions have not been fully defined. A previous study found Cables is located on human chromosome 18q11-12. Loss of Cables expression as determined by immunohistochemical staining (IHC) occurred in 60-70% of sporadic colorectal cancers that were usually correlated to loss of heterozygosity at 18q. To determine if Cables is an important target for the chromosome 18q deletions, the susceptibility of Cables-/- mice to develop colon tumors was studied. A well characterized colonic carcinogen, 1,2-dimethylhydrazine (DMH) was used as a tumor initiator. Cables-/- mice (n=25) and the Cables+/+ littermates (n=25) were treated with subcutaneous DMH injections over 20 weeks to initiate tumorigenesis. The median survival after DMH injections was significantly shorter for the Cables-/- mice compared to Cables+/+ littermates. The total number of colorectal tumors that developed in the Cables-/- mice was 46 tumors versus 21 tumors. The increased numbers of colorectal tumors, as well as shorter survival of the Cables-/- mice provides compelling evidence that Cables could play an important role in the pathogenesis and progression of colon cancer in mice. These data coupled with previous observations support the hypothesis that Cables is a relevant target of the chromosome 18q deletions frequently seen in human colorectal cancer.

Prevalence and relative risk of malignancy in relatives of inflammatory bowel disease patients and control subjects.

The relation between inflammatory bowel disease (IBD) and colorectal cancer (CRC) is not clearly defined. Some investigators suggest that patients with extensive colitis have a genetic predisposition to CRC and that long-standing inflammation is not of primary importance in the promotion of cancer. We have assessed any increased risk of colon cancer in the relatives of IBD patients. We studied the prevalence of malignancy in the relatives of 251 IBD patients [198 ulcerative colitis (UC); 53 Crohn's disease of the colon (CDC)] and 251 orthopedic patients (ORTHO) as controls. In all patients (UC, CDC) as well as in controls (ORTHO) the prevalence of colon, extracolic digestive and extradigestive malignant tumors in the first-degree relatives was evaluated. We found no significant difference in the number of colorectal tumors or of tumors of any other kind in the diverse group of relatives of patients with IBD and ORTHO patients. Our data do not point to the existence of hereditary factors linking UC or CDC to CRC.