Background: Herein, we review the Cotton Top Tamarin (CTT), Saguinus oedipus, a unique spontaneous model for colorectal cancer (CRC). Despite its predisposition to inflammatory bowel disease (IBD) and frequent development of CRC, the CTT is adept at avoiding colorectal metastasis in the liver. In contrast, the common marmoset (CM), Callithrix jacchus, is a natural negative control, in that it also contracts IBD, but usually not CRC. We review our findings in these New World monkeys in terms of the expression of CEACAM adhesion models and their related molecules to contrast them with human disease. Methods: Specimens were collected from aforementioned monkey colorectal and other tissues, colonic washings, serum for analysis of tissue extraction, and colonic washings via ELISA, using a battery of antibodies. Fixed tissues were analyzed using immunohistochemistry and CEACAMs were extracted via Western blotting. Serum CEA levels were analyzed using ELISA, and DNA was extracted via a Bigblast genomics sequencing kit. Results: Serum CEA was significantly elevated in CTTs, and one-third of them die from CRC. Unlike others, we were unable to stain for CEA in tissues. The sialylated carbohydrate antigen recognized by monoclonal antibody (MAb) SPAN-1 does stain in 16.7% of CTT tissues, but the anti-aminoproteoglycan MAb, CaCo.3/61, stained 93.3% (OR70·00[CI6.5-754.5] p < 0.0001). The common CEA kits from Abbott and Roche were non-conclusive for CEA. We later adopted a CEA AIA-PACK from Tosoh Medics, which identified a 50 Kda band via Western blotting in humans and CTTs. The CEA levels were higher using the CEA AIA-PACK than the Pharmatrope kit (932 ± 690 versus 432 ± 407 ng/mL (p < 0.05)) in human patient colonic effluent, not statistically significant (NSS) for CTT extracts or effluent (733 ± 325 and 739 ± 401 ng/mL, respectively). It was suggested that the smaller CTT CEA moiety might lack components that facilitate the spread of liver metastasis. Later, using more specific CEA assays and increased numbers of specimens, we were able to show higher CEA serum expression in CTTs than in CMs (632.1 ± 306.1 vs. 81.6 ± 183.6, p < 0.005), with similar differences in the serum samples. Western blotting with the anti-CEA T84.66 MAb showed bands above 100 KDa in CTTs. The profiles in CTTs were similar to human patients with inflammatory bowel disease. We established that the CEA anchorage to the cell was a GPI-linkage, advantageous for the inhibition of differentiation and anoikis. With further CEA DNA analysis, we were able to determine at least five different mechanisms that may inhibit liver metastasis, mostly related to CEA, but later expanded this to seven, and increased the relationships to CEACAM1 and other related molecules. Recently, we obtained CTT liver mRNA transcriptomes that implicated several pathways of interest. Conclusions: With efforts spanning over three decades, we were able to characterize CEA and other changes that allow us to better understand the CTT phenomenon of liver metastasis inhibition. We are in the process of characterizing the CTT liver mRNA transcriptome to compare it with that of the common marmoset. Currently, liver CTT gene expression patterns suggest that ribosomes, lipoproteins, and antioxidant defense are related to differences between CTTs and CMs.

This paper aims to explore the diagnostic value of enhanced magnetic resonance imaging (MRI) combined with a carcinoembryonic antigen (CEA) and carbohydrate antigen in terms of the liver metastasis of colorectal cancer.

A total of 167 colorectal cancer patients with liver metastasis and 167 colorectal cancer patients without liver metastasis were selected as the subjects. An automatic electrochemiluminescence analyser was then used to detect the tumour markers CEA, CA19-9, CA125 and CA72-4. The consistency between the MRI examination and clinical pathological examination was also analysed, and the sensitivity, specificity and positive and negative predictive values of various combined detection methods were compared.

The abnormal rates of CEA, CA19-9, CA125 and CA72-4 in the two groups were statistically significant (P < 0.05), while the results of the enhanced MRI and clinicopathological examination for liver metastasis in patients with colon cancer were largely consistent (Kappa coefficient = 0.788, P < 0.000). However, the two methods were inconsistent. The false positive rate of the enhanced MRI examination was 15.3%, while the false negative rate was 6.0%. The specificity (94.61%), positive predictive value (92.68%) and positive likelihood ratio (12.67%) were the highest for the MRI combined with serial CEA, while the sensitivity (98.80%) and negative predictive value (97.22%) were the highest with the MRI combined with parallel CEA, and this combination returned the lowest negative likelihood ratio (0.03).

The combination of MRI and CEA excludes non-metastatic patients and identifies colorectal liver metastasis cancer patients. Overall, it has a higher diagnostic value.

Colorectal cancer (CRC) is a common cause of cancer-related deaths largely due to CRC liver metastasis (CRLM). Identification of targetable mechanisms continues and includes investigations into the role of inflammatory pathways. Of interest, MAPK is aberrantly expressed in CRC patients, yet the activation status is not defined. The present study assessed p38γ activation in CRC patients, cancer cells, and tissues of cotton top tamarin (CTT) and common marmoset (CM). The primate world is an overlooked resource as colitis-CRC-prone CTT are usually inure to liver metastasis while CM develop colitis but not CRC. The results demonstrate that p38γ protein and phosphorylation levels are significantly increased in CRC patients compared to normal subjects and CTT. Furthermore, p38γ phosphorylation is significantly elevated in human CRC cells and hepatoblastoma cells but not in CM colon. Additionally, carcinoembryonic antigen (CEA) and biliary glycoprotein (BGP) are induced in the CRC patients that showed p38γ phosphorylation. Inhibition of p38 MAPK in CRC cells showed a significant decline in cell growth with no effect on apoptosis or BGP level. Overall, p38γ is activated in CRC tumorigenesis and likely involves CEA antigens during CRLM in humans but not in the CTT or CM, that rarely develop CRLM.

1,2-dimethylhydrazine (DMH) is a member in the class of hydrazines, strong DNA alkylating agent, naturally present in cycads. DMH is widely used as a carcinogen to induce colon cancer in animal models. Exploration of DMH-induced colon carcinogenesis in rodent models provides the knowledge to perceive the biochemical, molecular, and histological mechanisms of different stages of colon carcinogenesis. The procarcinogen DMH, after a series of metabolic reactions, finally reaches the colon, there produces the ultimate carcinogen and reactive oxygen species (ROS), which further alkylate the DNA and initiate the development of colon carcinogenesis. The preneolpastic lesions and histopathological observations of DMH-induced colon tumors may provide typical understanding about the disease in rodents and humans. In addition, this review discusses about the action of biotransformation and antioxidant enzymes involved in DMH intoxication. This understanding is essential to accurately identify and interpret alterations that occur in the colonic mucosa when evaluating natural or pharmacological compounds in DMH-induced animal colon carcinogenesis.

Much has been written about hepatic metastasis and animal models abound. In terms of the human experience, progress in treating this final common pathway, a terminal event of many human malignancies has been relatively slow. The current thinking is that primary prevention is best served by early detection of cancer and eradication of early stage cancers by screening. Some cancers spread early in their course and the role of screening may be limited. Until relatively recently there has not been a pathfinder model that makes the evasion of this unfortunate event a reality. This review discusses such an animal model and attempts to relate it to human disease in terms of intervention. Concrete proposals are also offered on how scientists may be able to intervene to prevent this deadly progression of the cancer process.