Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis

Giardiello, Francis M.; Casero, Robert A.; Hamilton, Stanley R.; Hylind, Linda M.; Trimbath, Jill D.; Geiman, Deborah E.; Judge, Katharine R.; Hubbard, Walter C.; Offerhaus, G.J.A.; Yang, Vincent W.

doi:10.1053/j.gastro.2003.11.013

Cited by 87 publications

(86 citation statements)

References 33 publications

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“…The APC Min mouse, because of a germ-line mutation in the APC tumor suppression gene, exhibits a high incidence of intestinal adenomas resembling clinical early-onset FAP syndrome (9,10). In recent years, the APC Min model has provided important mechanistic leads for the preventive efficacy of several classes of synthetic pharmacological agents, including non-streroidal anti-inflammatory drugs (NSAIDs), selective enzyme inhibitors, growth factor receptor antagonists and small molecule inhibitors (29,32,(42)(43)(44)(45)(46)(47)(48)(49). These observations have demonstrated a direct correlation between the modulation of pathogenesis and the relevant molecular target for efficacy.…”

Section: Modulation Of Carcinogenesismentioning

confidence: 99%

Prevention of early-onset familial/hereditary colon cancer: New models and mechanistic biomarkers (Review)

Telang

Guo²,

Katdare³

2006

Int J Oncol

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Abstract. Human colon cancer is a multi-factorial, multi-step disease wherein genetic and dietary factors represent important regulators of initiation, promotion and progression. While the etiology of sporadic colon cancer remains largely unidentified, familial adenomatous polyposis (FAP) and hereditary non-polyposis colon cancer (HNPCC) represent predisposing genetic syndromes for early-onset familial/hereditary colon cancer. These syndromes are characterized by germ-line mutations in the adenomatous polyposis coli (APC) and/or DNA mismatch repair genes, respectively. Currently available preclinical animal models for human FAP and HNPCC syndromes, expressing clinically relevant germ-line mutations, exhibit adenomas in the small intestine rather than in the colorectum. These models are, therefore, subject to extrapolation for direct clinical translatability of the data for colon carcinogenesis and chemoprevention. Experimental models expressing clinically relevant genetic defects (APC and/or DNA mismatch repair gene mutations) in an appropriate target site (colon) may represent novel approaches that reduce extrapolation of the data for their clinical relevance. This report provides an overview on carcinogenesis and chemoprevention in preclinical models of FAP and HNPCC syndromes, and summarizes recent data on i) development of new cell culture models for FAP and HNPCC syndromes; and ii) validation of developed models for rapid, mechanism-based screening of new pharmacological or naturally occurring chemopreventive agents.

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Section: Modulation Of Carcinogenesismentioning

confidence: 99%

Prevention of early-onset familial/hereditary colon cancer: New models and mechanistic biomarkers (Review)

Telang

Guo²,

Katdare³

2006

Int J Oncol

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“…However, these interventional strategies are associated with adverse toxic side effects that compromise patient compliance (29)(30)(31)(32).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, minimally toxic natural dietary components may also modulate the efficacy of toxic chemotherapeutic drugs (35). On the mechanistic level, DFMO functions as a selective inhibitor of ornithine decarboxylase which is an established early response gene and a rate limiting enzyme for the biosynthesis of polyamines (30,31), SUL is a non-selective cyclooxygenase inhibitor (34), EGCG is demonstrated to affect EGF signaling (36), while EPA functions as an inhibitor of lipoxygenase, a critical enzyme for production of leukotrienes (33). All of these targets are known to play important roles in colon carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome

Telang¹

2009

Oncol Rep

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Abstract. Clinical familial adenomatous polyposis (FAP) syndrome represents a high risk pre-invasive precursor for colon cancer, and is characterized by germ line mutation in the adenomatous polyposis coli (APC) tumor suppressor gene. Cellular models with relevant genetic and biological characteristics should provide important mechanistic leads for predisposition and preventive intervention. Cloned colon epithelial cell line from the Apc 850 Min /+ mouse represented a model for FAP. Cell cycle progression, cellular apoptosis and anchorage-independent growth represented the biomarkers for carcinogenic risk. The Apc mutant 850Min COL-Cl 1 cells exhibited decreased G 0 /G 1 :S+G 2 /M ratio, increased S+G 2 /M: subG 0 ratio, and increased anchorage-independent colony formation, indicating loss of homeostatic growth control and gain of anchorage-independent growth. Growth of these cells in serum-depleted medium was promoted by mitogenic insulin and epidermal growth factor, and inhibited by antimitogenic transforming growth factor-ß 1 and dexamethasone. Treatment with low dose combinations of synthetic enzyme inhibitor difluoro methylornithine (DFMO), synthetic nonsteroidal anti-inflammatory drug sulindac (SUL), and naturally occurring epigallocatechin gallate (EGCG), and eicosapentaenoic acid (EPA) produced cytostatic growth arrest and inhibited anchorage-independent colony formation. These data identify a novel cell culture model and validate a mechanism-based approach to prioritize combinations of effective chemopreventive compounds for prevention/therapy of colon cancer.

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“…Sulindac inhibits colorectal carcinogenesis in rodent models (9,10) and causes regression of adenomas (2,11) in patients with familial adenomatous polyposis coli. The mechanism by which this activity occurs is unclear, although some correlation has been found between sulindac treatment and reduced levels of prostaglandins in the human colorectal mucosa (12,13). In relation to reduced prostaglandin levels, sulindac treatment was not found to be chemopreventive in all studies (2,13).…”

Section: Introductionmentioning

confidence: 98%

“…The mechanism by which this activity occurs is unclear, although some correlation has been found between sulindac treatment and reduced levels of prostaglandins in the human colorectal mucosa (12,13). In relation to reduced prostaglandin levels, sulindac treatment was not found to be chemopreventive in all studies (2,13). In addition, several studies indicate that sulindac and its metabolites have demonstrated chemoprotective effects through inhibition of angiogenesis (14,15).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of sulindac on DMBA-induced hamster cheek pouch carcinogenesis and its derived cell line

Urade¹

2009

Oncol Rep

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Prostanoids, ornithine decarboxylase, and polyamines in primary chemoprevention of familial adenomatous polyposis

Cited by 87 publications

References 33 publications

Prevention of early-onset familial/hereditary colon cancer: New models and mechanistic biomarkers (Review)

Prevention of early-onset familial/hereditary colon cancer: New models and mechanistic biomarkers (Review)

Novel cell culture model for prevention of carcinogenic risk in familial adenomatous polyposis syndrome

Inhibitory effect of sulindac on DMBA-induced hamster cheek pouch carcinogenesis and its derived cell line

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