Colorectal cancer neoplasia

Selective COX-2 inhibitors have also been shown to prevent early and late forms of colorectal neoplasia in rat models. Reddy et al. showed that administration of celecoxib inhibited aberrant colonic crypt foci (ACF) induction and multiplicity by about 40-49% in an azoxymethane-induced ACF rat model (81). Later the same investigators also showed that dietary administration of celecoxib can inhibit both the incidence and multiplicity of colon tumors by about 93 % and 97 %, respectively in the same rat model (82). Other researchers reported similar results with the Min mouse model (52). There is little data on human clinical trials with selective COX-2 inhibitors for colorectal tumor prevention. Recently Steinbach et al. conducted a double-blind, placebo-controlled study with 77 patients with FAP, and reported that treatment with celecoxib, a selective COX-2 inhibitor, for 6 mo led to a significant reduction (28%) in the number of colorectal polyps in these patients (50). Collectively, COX-2 nonspecific or specific NSAIDs appear to have chemopreventive activity against colorectal cancer development. Selective... 

However, the impact of Cryptosporidium species in human health could be still more important. Actually, we have reported recently that C. parvum is able to induce intestinal adenocarcinoma in SCID mice (Certad et al. 2007). This is the first demonstration of the ability of an Apicomplexan parasite to induce neoplastic lesions in an epithelinm. We do not know if C. parvum is able to cause intestinal neoplasia in hnmans, but a recent survey reported a high frequency of Cryptosporidium infection in patients with colorectal cancer (Sulzyc-Bielicka et al. 2007). 

Colorectal cancer MiR-19a,miR-21,miR-29a,miR-92,miR-148a,and miR-200b up MiR-30c,miR-133a,and miR-145 down Real-time PCR miRNA profiles has relevance to the biological and clinical behavior of colorectal neoplasia 58... 

Bandres et al. examined the expression of 156 mature miRNA in colorectal cancer by real-time PCR and the results suggested that miRNA expression profile could be relevant to the biological and clinical behavior of colorectal neoplasia [58]. Michael et al. identified 28 different miRNAs in a colonic adenocarcinoma and normal mucosa by using miRNA cloning and northern blotting. They also indicated that miR-143 and miR-145 are downregulated in cells derived from breast, prostate, cervical, and lymphoid cancers as well as colorectal tumors [59]. 

Hawcroft, G., Loadman, P.M., Belluzzi, A. and Hull, M.A. (2010) Effect of eicosapen-taenoic acid on E-type prostaglandin synthesis and EP4 receptor signaling in human colorectal cancer cells. Neoplasia 12, 618-627. 

A recent smdy examined the level of DiAcSpm in colorectal cancer and intraepithelial neoplasia tissues (Kuwata et al. 2013). DiAcSpm was very scant in normal tissues but was markedly increased in resected stage II, HI, and IV colon cancer tissues. The level of DiAcSpm was also maikedly elevated in metastatic liver lesions in individuals with stage IV colon cancer compared to adjacent normal tissue. HPLC analysis indicated that the levels of Af-acetylspermidine and Af-acetylspermine are also increased in cancer tissues. This is the first report that definitively identifies the presence of DiAcSpm in human tissues. Importantly, DiAcSpm is markedly increased in tumor tissue compared to normal tissue. The levels of A/ -acetylspermidine and Af, V -diacetylspermidine were very low or undetectable in normal tissues and were not significantly increased in cancer tissues. 

Trans-Isomers and Cancer A study conducted in postmenopausal women suggested an association between risk of breast cancer and the level of hydrogenated oil derived mono-frawi-fatty acids was stored in the adipose tissue (221). It was also found that frawi-fatty acid might cause colorectal neoplasia by interfering with the cell membrane function or eicosanoid metabolism (222). Increased adenoma prevalence was associated with the consumption of sweetened baked goods, oils, and condiments. 

Matthew, J.A., Fellows, I.W., Prior, A., Kennedy, H.J., Bobbin, R., and Johnson, I.T., Habitual intake of fruits and vegetables amongst patients at increased risk of colorectal neoplasia. Cancer Lett., 114,255-258,1997. 

Michael MZ, SM OC, van Holst Pellekaan NG, Young GP, James RJ 2003. Reduced accumulation of specific microRNAs in colorectal neoplasia. Mol Cancer Res 1(12) 882-891. 

Another area worthy of future investigation is the treatment of non-colorectal, non-neuroendocrine cancers metastatic to the liver. Often referred to as mixed neoplasia, these refer to patients with liver-dominant metastatic disease to the liver from various primaries (breast, melanoma, pancreas, and lung). Although several reports have been described, controlled phase II studies using time-to-progression, tumor response, or progression-free-survival would be clinically relevant given the dearth of options for some of these patients [51-54]. 

Reduced accumulation of specific microRNAs in colorectal neoplasia. Molecular Cancer Research, 1, 882-91. 

---