Colon Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Colon Cancer, including details on causes, treatment, symptoms.

Organ-specific inhibition of metastatic colon carcinoma by CXCR3 antagonism.

Cambien B, Karimdjee BF, Richard-Fiardo P, Bziouech H, Barthel R, Millet MA, Martini V, Birnbaum D, Scoazec JY, Abello J, Al Saati T, Johnson MG, Sullivan TJ, Medina JC, Collins TL, Schmid-Alliana A, Schmid-Antomarchi H

Université de Nice Sophia Antipolis, UFR Sciences, Nice F-06002, France.

Liver and lung metastases are the predominant cause of colorectal cancer (CRC)-related mortality. Recent research has indicated that CXCR3/chemokines interactions that orchestrate haematopoetic cell movement are implicated in the metastatic process of malignant tumours, including that of CRC cells to lymph nodes. To date, however, the contribution of CXCR3 to liver and lung metastasis in CRC has not been addressed. To determine whether CXCR3 receptors regulate malignancy-related properties of CRC cells, we have used CXCR3-expressing CRC cell lines of human (HT29 cells) and murine (C26 cells) origins that enable the development of liver and lung metastases when injected into immunodeficient and immunocompetent mice, respectively, and assessed the effect of CXCR3 blockade using AMG487, a small molecular weight antagonist. In vitro, activation of CXCR3 on human and mouse CRC cells by its cognate ligands induced migratory and growth responses, both activities being abrogated by AMG487. In vivo, systemic CXCR3 antagonism by preventive or curative treatments with AMG487 markedly inhibited the implantation and the growth of human and mouse CRC cells within lung without affecting that in the liver. In addition, we measured increased levels of CXCR3 and ligands expression within lung nodules compared with liver tumours. Altogether, our findings indicate that activation of CXCR3 receptors by its cognate ligands facilitates the implantation and the progression of CRC cells within lung tissues and that inhibition of this axis decreases pulmonary metastasis of CRC in two murine tumour models.

Published 5 June 2009 in Br J Cancer, 100(11): 1755-64.
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Articles on Colon Cancer published 4 June 2009:

Association of common genetic variants in SMAD7 and risk of colon cancer.   Carcinogenesis, 30(6): 982-6.

Two recent genome-wide association studies (GWAS) identified three common variants in SMAD7 (rs4464148, rs4939827 and rs12953717) that confer modest susceptibility to colorectal cancer. Here, we replicated the association of rs4464148 with colon cancer in a population-based case-control study (561 cases and 721 controls). Compared with the TT genotype, those with CT and CC had an adjusted odds ratio (OR) and 95% confidence interval of 1.06 (0.82-1.38) and 1.86 (1.17-2.96), respectively ... [Abstract] [Full-text]

Promoter CpG island hypermethylation- and H3K9me3 and H3K27me3-mediated epigenetic silencing targets the deleted in colon cancer (DCC) gene in colorectal carcinogenesis without affecting neighboring genes on chromosomal region 18q21.   Carcinogenesis, 30(6): 1041-8.

Chromosomal loss of 18q21 is a frequent event in colorectal cancer (CRC) development, suggesting that this region harbors tumor suppressor genes (TSGs). Several candidate TSGs, among which methyl-CpG-binding domain protein 1 (MBD1), CpG-binding protein CXXC1, Sma- and Mad-related protein 4 (SMAD4), deleted in colon cancer (DCC) and methyl-CpG-binding domain protein 2 (MBD2) are closely linked on a 4-Mb DNA region on chromosome18q21. As TSGs can be epigenetically silenced, this study ... [Abstract] [Full-text]

Articles on Colon Cancer published 3 June 2009:

Development and validation of a colon cancer risk assessment tool for patients undergoing colonoscopy.   Am J Gastroenterol, 104(6): 1508-18.

OBJECTIVES: Diagnostic criteria for hereditary colorectal cancer (CRC) are complex. "Open-access" colonoscopy makes it challenging to identify who needs genetic evaluation, intensive surveillance, and screening for extracolonic tumors. Our aim was to develop a simple, preprocedural risk assessment tool to identify who may be at highest risk for CRC. METHODS: A total of 631 outpatients undergoing colonoscopy at two academic practices completed a questionnaire assessing personal and ... [Abstract] [Full-text]

Combining autofluorescence imaging and narrow-band imaging for the differentiation of adenomas from non-neoplastic colonic polyps among experienced and non-experienced endoscopists.   Am J Gastroenterol, 104(6): 1498-507.

OBJECTIVES: Endoscopic tri-modal imaging incorporates high-resolution white-light endoscopy (HR-WLE), narrow-band imaging (NBI), and autofluorescence imaging (AFI). Combining these advanced techniques may improve endoscopic differentiation between adenomas and non-neoplastic polyps. In this study, we aimed to assess the interobserver variability and accuracy of HR-WLE, NBI, and AFI for polyp differentiation and to evaluate the combined use of AFI and NBI. METHODS: First, still images of 50 ... [Abstract] [Full-text]

A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene.   Cell, 137(5): 835-48.

Oncogenic mutations in the small GTPase Ras are highly prevalent in cancer, but an understanding of the vulnerabilities of these cancers is lacking. We undertook a genome-wide RNAi screen to identify synthetic lethal interactions with the KRAS oncogene. We discovered a diverse set of proteins whose depletion selectively impaired the viability of Ras mutant cells. Among these we observed a strong enrichment for genes with mitotic functions. We describe a pathway involving the mitotic kinase ... [Abstract] [Full-text]

Effect of RasGAP N2 fragment-derived peptide on tumor growth in mice.   J Natl Cancer Inst, 101(11): 828-32.

Peptides that interfere with the natural resistance of cancer cells to genotoxin-induced apoptosis may improve the efficacy of anticancer regimens. We have previously reported that a cell-permeable RasGAP-derived peptide (TAT-RasGAP(317-326)) specifically sensitizes tumor cells to genotoxin-induced apoptosis in vitro. Here, we examined the in vivo stability of a protease-resistant D-form of the peptide, RI.TAT-RasGAP(317-326), and its effect on tumor growth in nude mice bearing subcutaneous ... [Abstract] [Full-text]

Articles on Colon Cancer published 2 June 2009:

Metastasis to the sigmoid or sigmoid mesenteric lymph nodes from rectal cancer.   Ann Surg, 249(6): 960-4.

OBJECTIVE: We analyzed metastases to the sigmoid and sigmoid mesenteric lymph nodes from rectal cancer. BACKGROUND: It has been reported that rectal cancer spreads upward and lateral. However, metastasis to the sigmoid mesenteric or sigmoid nodes from rectal cancer has been rarely reported. METHODS: We enrolled 347 patients who underwent curative resection for rectal cancer with proven lymph node metastases and dissection of the sigmoid and sigmoid mesenteric lymph nodes. Lymph node ... [Abstract] [Full-text]

Tobacco-specific carcinogen enhances colon cancer cell migration through alpha7-nicotinic acetylcholine receptor.   Ann Surg, 249(6): 978-85.

OBJECTIVE: To study the mechanism of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-enhanced migration of colon cancer cells. BACKGROUND DATA: Long-term cigarette smoking increases the risk of colorectal cancer mortality. Tobacco-specific carcinogen, NNK, was reported to increase DNA synthesis of colon cancer cells. Since metastasis is the major cause of cancer death, the influence of NNK on the migration of colon cancer cells remains to be determined. METHODS: Receptor for NNK in colon ... [Abstract] [Full-text]

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