[1]
Farida Elmoursi Elbassiouni, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt.
[2]
Elsayed Ibrahim Salim, Department of Zoology, Faculty of Science, Tanta University, Tanta, Egypt.
[3]
Doaa Hussein Zineldeen, Department of Biochemistry, Faculty of Medicine, Tanta University, Tanta, Egypt.
Colon carcinogenesis is a multistep process which originates from a series of histopathological and molecular alterations. To study the effect of the combination of Cetuximab (Erbitux™) and Sodium butyrate and the role of mucous secreting cells during short –term rat colon carcinogenesis, we used male Wistar rats divided into 5 groups. Group 1: Normal control rats, group 2: 1,2-dimethylhydrazine (DMH)- injected rats, group 3: Rats injected with DMH then received Cetuximab at a dose of 10 mg/kg body weight for two weeks in the 5th and 8th week of start, group 4: Rats injected with DMH then treated with Na-butyrate, i.p, 200mg/kg body weight from the 5th week till the end, and group 5: Rats injected with DMH then treated with both Cetuximab and Na-butyrate at the same doses and protocols as in groups 3 and 4. The rats from groups 3, 4 had significantly lower numbers of colonic cancer biomarkers; namely aberrant crypt foci (ACF) and mucin depleted foci (MDF) as compared with DMH group 2. Interestingly, the Cetuximab and Na-Butyrate-treated group 5 had significantly the lowest numbers of ACF and MDF as compared with DMH control, as well as retained the goblet cell numbers in the colonic crypts almost to control levels.
Colon Carcinogenesis, Cetuximab, Erbitux, Sodium Butyrate, Aberrant Crypt Foci, Mucin Depleted Foci
[1]
Ansil, P. N., et al. (2013). "Chemopreventive effect of Amorphophallus campanulatus (Roxb.) blume tuber against aberrant crypt foci and cell proliferation in 1, 2-dimethylhydrazine induced colon carcinogenesis." Asian Pacific journal of cancer prevention: APJCP 14 (9): 5331-5339.
[2]
Bancroft, J. D. and M. Gamble (2008). Theory and practice of histological techniques, Elsevier Health Sciences.
[3]
Bancroft, J. D. and C. Layton (2013). "The Hematoxylin and eosin." Theory & Practice of histological techniques. 7th ed., Churchill Livingstone of El Sevier, Philadelphia: 173-214.
[4]
Bird, R. P. (1995). "Role of aberrant crypt foci in understanding the pathogenesis of colon cancer." Cancer Letters 93 (1): 55-71.
[5]
Bird, R. P. and C. K. Good (2000). "The significance of aberrant crypt foci in understanding the pathogenesis of colon cancer." Toxicology Letters 112-113: 112-113.
[6]
Brehm, A., et al. (1998). "Retinoblastoma protein recruits histone deacetylase to repress transcription." Nature. 391 (6667): 597.
[7]
Caderni, G., et al. (2003). "Identification of Mucin-depleted Foci in the Unsectioned Colon of Azoxymethane-treated Rats: Correlation with Carcinogenesis." Cancer Research 63: 2388-2392.
[8]
Chen, H.-M., et al. (2013). "Identification of Potential Target Genes of Butyrate in Dimethylhydrazine-Induced Colorectal Cancer in Mice." Nutrition and Cancer 65 (8): 1171-1183.
[9]
Citri, A. and Y. Yarden (2006). "EGF-ERBB signalling: towards the systems level." Nature reviews. Molecular cell biology 7 (7): 505-516.
[10]
Cone, R. A. (2009). "Barrier properties of mucus." Adv. Drug Deliv. Rev. Advanced Drug Delivery Reviews 61 (2): 75-85.
[11]
Crim, K. C., et al. (2008). "Upregulation of p21Waf1/Cip1 expression in vivo by butyrate administration can be chemoprotective or chemopromotive depending on the lipid component of the diet." Carcinogenesis Carcinogenesis 29 (7): 1415-1420.
[12]
Davie, J. R. (2003). "Nutritional Proteomics in Cancer Prevention - Inhibition of Histone Deacetylase Activity by Butyrate." The Journal of nutrition. 133 (7): 2485S.
[13]
Donohoe, Dallas R., et al. (2011). "The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon." Cell Metabolism Cell Metabolism 13 (5): 517-526.
[14]
Donohoe, D. R., et al. (2011). "The Microbiome and Butyrate Regulate Energy Metabolism and Autophagy in the Mammalian Colon." CELL METABOLISM 13 (5): 517-526.
[15]
Dyson, J. E., et al. (1992). "The effect of sodium butyrate on the growth characteristics of human cervix tumour cells." British journal of cancer 65 (6): 803-808.
[16]
Femia, A. P., et al. (2007). "Frequent mutation of Apc gene in rat colon tumors and mucin-depleted foci, preneoplastic lesions in experimental colon carcinogenesis." Cancer Research 67 (2): 445-449.
[17]
Femia, A. P., et al. (2012). "Mucin Depleted Foci, Colonic Preneoplastic Lesions Lacking Muc2, Show Up-Regulation of Tlr2 but Not Bacterial Infiltration." PLoS ONE PLoS ONE 7 (1): e29918.
[18]
Gunning, A. P., et al. (2013). "Mining the "glycocode" - Exploring the spatial distribution of glycans in gastrointestinal mucin using force spectroscopy." FASEB J. FASEB Journal 27 (6): 2342-2354.
[19]
Herbst, R. S., et al. (2005). "IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer." Expert Opinion on Biological Therapy Expert Opinion on Biological Therapy 1 (4): 719-732.
[20]
Hong, M. Y., et al. (2015). "In vivo regulation of colonic cell proliferation, differentiation, apoptosis, and P27Kip1 by dietary fish oil and butyrate in rats." Cancer Prev. Res. Cancer Prevention Research 8 (11): 1076-1083.
[21]
Jänne, P. A. and R. J. Mayer (2000). "Chemoprevention of colorectal cancer." The New England journal of medicine 342 (26): 1960-1968.
[22]
Kelman, Z., et al. (1999). "The C-terminal region of Schizosaccaromyces pombe proliferating cell nuclear antigen is essential for DNA polymerase activity." Proceedings of the National Academy of Sciences of the United States of America 96 (17): 9515-9520.
[23]
Kumar, A., et al. (2005). "Chromatin Remodeling Is a Key Mechanism Underlying Cocaine-Induced Plasticity in Striatum." Neuron Neuron 48 (2): 303-314.
[24]
Lenz, H. J., et al. (2006). "Multicenter Phase II and Translational Study of Cetuximab in Metastatic Colorectal Carcinoma Refractory to Irinotecan, Oxaliplatin, and Fluoropyrimidines." Journal of Clinical Oncology 24 (30): 4914-4921.
[25]
Lupton, J. R. (2004). "Microbial degradation products influence colon cancer risk: the butyrate controversy." The Journal of nutrition 134 (2): 479-482.
[26]
Lupton, J. R. (2004). "Symposium - Diet Induced Changes in the Colonic Environment and Colorectal Cancer - Microbial Degradation Products Influence Colon Cancer Risk: The Butyrate Controversy." The Journal of nutrition. 134 (2): 479.
[27]
Marks, P. A. and M. Dokmanovic (2005). "Histone deacetylase inhibitors: discovery and development as anticancer agents." Expert opinion on investigational drugs 14 (12): 1497-1511.
[28]
Maurin, N., et al. (2007). "Progression of tumors arising from large ACF is associated with the MUC5AC expression during rat colon MNNG carcinogenis." International Journal of Cancer 120 (3): 477-483.
[29]
Mc, M. J. (1946). "Histological demonstration of mucin after periodic acid." Nature 158.
[30]
McAuley, J. L., et al. (2007). "Research articles - MUC1 cell surface mucin is a critical element of the mucosal barrier to infection." The journal of clinical investigation. 117 (8): 2313.
[31]
McGinley, J. N., et al. (2011). "A Method for Serial Tissue Processing and Parallel Analysis of Aberrant Crypt Morphology, Mucin Depletion, and Beta-Catenin Staining in an Experimental Model of Colon Carcinogenesis." Biol Proced Online Biological Procedures Online 12 (1): 9032.
[32]
Mitsudomi, T. and Y. Yatabe (2010). "Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer." FEBS Journal 277 (2).
[33]
Monneret, C. (2007). "Histone deacetylase inhibitors for epigenetic therapy of cancer." Anti-cancer drugs 18 (4): 363-370.
[34]
Nautiyal, J., et al. (2012). "EGFR regulation of colon cancer stem-like cells during aging and in response to the colonic carcinogen dimethylhydrazine." American journal of physiology. 302 (4): G655.
[35]
Papanikolaou, A., et al. (2000). "Sequential and morphological analyses of aberrant crypt foci formation in mice of differing susceptibility to azoxymethane-induced colon carcinogenesis." Carcinogenesis 21 (8): 1567-1572.
[36]
Quintana-Hayashi, M. P., et al. (2015). "The Levels of Brachyspira hyodysenteriae Binding to Porcine Colonic Mucins Differ between Individuals, and Binding Is Increased to Mucins from Infected Pigs withDe NovoMUC5AC Synthesis." Infect. Immun. Infection and Immunity 83 (4): 1610-1619.
[37]
Raben, D., et al. (2003). "Understanding the mechanisms of action of EGFR inhibitors in NSCLC: what we know and what we do not know." Lung cancer (Amsterdam, Netherlands) 41: 15-22.
[38]
Raju, J. (2008). "Azoxymethane-induced rat aberrant crypt foci: Relevance in studying chemoprevention of colon cancer." World Journal of Gastroenterology 14 (43): 6632-6635.
[39]
Robbe, C., et al. (2004). "Structural diversity and specific distribution of O-glycans in normal human mucins along the intestinal tract." Biochem. J. Biochemical Journal 384 (2): 307-316.
[40]
Seshacharyulu, P., et al. (2012). "Targeting the EGFR signaling pathway in cancer therapy." Expert opinion on therapeutic targets 16 (1): 15-31.
[41]
Son, D. J., et al. (2015). "Synergistic Inhibitory Effects of Cetuximab and Cisplatin on Human Colon Cancer Cell Growth via Inhibition of the ERK-Dependent EGF Receptor Signaling Pathway." BioMed Res. Int. BioMed Research International 2015.
[42]
Sridhar, S. S., et al. (2003). "Inhibitors of epidermal-growth-factor receptors: a review of clinical research with a focus on non-small-cell lung cancer." LANCET ONCOLOGY 4 (7): 397-406.
[43]
Sylvester, P. A., et al. (2001). "Differential expression of the chromosome 11 mucin genes in colorectal cancer." J. Pathol. The Journal of Pathology 195 (3): 327-335.
[44]
Tammasakchai, A., et al. (2015). "Unpolished Thai Rice Prevents ACF Formation and Dysplastic Progression in AOM-Induced Rats and Induces Apoptosis Through Redox Alteration in CaCo-2 Cells." Asian Pacific journal of cancer prevention: APJCP 16 (7): 2827-2832.
[45]
Tanaka, T. (2009). "Colorectal carcinogenesis: Review of human and experimental animal studies." Journal of Carcinogenesis 8.
[46]
Tickoo, S. K., et al. (1998). "Colloidal iron staining in renal epithelial neoplasms, including chromophobe renal cell carcinoma: emphasis on technique and patterns of staining." The American journal of surgical pathology 22 (4): 419-424.
[47]
Wang, Z. (2016). "Transactivation of Epidermal Growth Factor Receptor by G Protein-Coupled Receptors: Recent Progress, Challenges and Future Research." International journal of molecular sciences 17 (1).
[48]
Xiao, M., et al. (2014). "Sodium Butyrate Induces Apoptosis of Human Colon Cancer Cells by Modulating ERK and Sphingosine Kinase 2." BES Biomedical and Environmental Sciences 27 (3): 197-203.
[49]
Zeeneldin, A. A., et al. (2013). "Small intestinal cancers among adults in an Egyptian district: A clinicopathological study using a population-based cancer registry." Journal of the Egyptian National Cancer Institute Journal of the Egyptian National Cancer Institute 25 (3): 107-114.
[50]
Zimmerman, M. A., et al. (2012). "Butyrate suppresses colonic inflammation through HDAC1-dependent Fas upregulation and Fas-mediated apoptosis of T cells." AJP: Gastrointestinal and Liver Physiology AJP: Gastrointestinal and Liver Physiology 302 (12): G1405-G1415.
