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Sulindac and Plant Compounds in Preventing Colon Cancer

ABSTRACT: RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. The use of sulindac may be an effective way to prevent colon cancer. Eating a diet rich in fruits and vegetables appears to reduce the risk of some types of cancer. Curcumin, rutin, and quercetin are compounds found in plants that may prevent the development of colon cancer. PURPOSE: Randomized clinical trial to study the effectiveness of sulindac, curcumin, rutin, and quercetin in preventing colon cancer.

DISEASE(S): Colon Cancer,Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2002901 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Expression data from murine colon tumors induced by azoxymethane. Tumors from control, obese, formerly obese, or sulindac-treated mice.

Project description:Obesity is associated with an increased risk of colon cancer. Our current study examines whether weight loss and/or treatment with the non-steroidal anti-inflammatory drug (NSAID) sulindac suppresses the protumor effects of obesity in a mouse model of colon cancer. Azoxymethane-treated male FVB/N mice were fed a low-fat diet (LFD) or high-fat diet (HFD) for 15 weeks, then HFD mice were randomized to remain on HFD (obese) or switch to LFD (formerly obese (FOb-LFD)). Within the control (LFD), obese, and FOb-LFD groups, half the mice were also randomized to start sulindac treatment (140 ppm in the diet). All mice were euthanized seven weeks later. FOb-LFD mice had intermediate levels of body weight, lower than obese but higher than control mice (P<0.05). Sulindac did not affect body weight. Obese mice had greater tumor multiplicity and burden than all other groups (P<0.05). Transcriptomic profiling indicated that both weight loss and sulindac modulate the expression of tumor genes related to invasion and may promote a more anti-tumor immune landscape. Furthermore, the fecal microbes Prevotella and Akkermansia muciniphila, both known to be elevated in colorectal cancer patients, were positively correlated with tumor multiplicity and reduced by sulindac in obese mice. In sum, either moderate weight loss or sulindac treatment completely reversed the effects of chronic obesity on colon tumorigenesis. Our findings suggest that an investigation regarding the effects of NSAID treatment on colon cancer risk and/or progression in obese individuals is warranted, particularly for those unable to achieve moderate weight loss.

2022-08-10 | GSE197846 | GEO

Effect of NO-sulindac treatment on hypoxic prostate cancer cells

Project description:The hypoxia response contributes to radio and chemo-resistance in cancer cells. Our previous work has shown that the nitric oxide donating non-steroidal anti-inflammatory drug (NO-NSAID) NO-sulindac is a potent inhibitor of the hypoxia response in prostate cancer cells and leads to increased susceptibilty to radiation. In this study we used microarrays to investigated the global impact of NO-sulindac on the hypoxia response in prostate cancer cells with a view to determining the mechanism of action. PC3 hormone-insensitive prostate cancer cells were grown under normoxic or hypoxic conditions and treated with NO-sulindac, unnitrated sulindac or vehicle control. Global gene expression in response to treatment was examined using microarrays and the bioconductor software suite. Gene set enrichment analysis (GSEA), Gene ontology (GO) analysis and pathway analysis were used to examine the biological impact of treatments.

2012-12-01 | E-GEOD-34112 | biostudies-arrayexpress

Effect of NO-sulindac treatment on hypoxic prostate cancer cells

2012-12-01 | GSE34112 | GEO

Comparison of Sulindac, Aspirin, and Ursodiol in Preventing Colorectal Cancer

Project description:RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development or recurrence of cancer. It is not yet known whether sulindac, aspirin, or ursodiol is more effective in preventing colorectal cancer. PURPOSE: This randomized phase II trial is studying how well sulindac works compared to aspirin or ursodiol in preventing colorectal cancer.

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Eflornithine and Sulindac in Preventing Colorectal Cancer in Patients With Colon Polyps

Project description:This randomized phase III trial is studying eflornithine and sulindac to see how well they work compared to a placebo in preventing colorectal cancer in patients with colon polyps. Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of eflornithine and sulindac may prevent colorectal cancer. It is not yet known whether eflornithine and sulindac are more effective than a placebo in preventing colorectal cancer

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Curcumin for the Prevention of Colon Cancer

Project description:RATIONALE: Chemoprevention therapy is the use of certain drugs to try to prevent the development of cancer. Curcumin may be effective in preventing the development of colon cancer. PURPOSE: Phase I trial to determine the dose amount of curcumin that can be tolerated to help in preventing colon cancer in healthy men and women.

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Transcription profiling by array of intestinal adenomas from Apc -/+ mice after sulindac treament

Project description:Transcriptional profile of tumors of ApcMin/+ mice after sulindac treatment

2008-06-03 | E-MEXP-1401 | biostudies-arrayexpress

Differential Chemopreventive Activity of Sulindac and/or Atorvastatin in Apc+/Min-FCCC Mice With or Without Colorectal Adenomas

Project description:Emerging data suggest that some high-risk subjects benefit more than others from preventive intervention. The goal of this study was to determine the efficacy of sulindac (Sul) and/or atorvastatin (Atorva) against spontaneous colorectal adenomas in Apc+/Min-FCCC mice in which the tumor-bearing status was known at the time of treatment initiation. Administration of Sul/Atorva to tumor-bearing mice led to a 43% reduction in the multiplicity of colorectal adenomas as compared to that of untreated tumor-bearing mice. Atorvastatin completely inhibited the formation of microadenomas in mice that were tumor-free at baseline, with associated decreases in the expression of inflammatory mediators observed. Expression of Hoxb13 and Rprm was enhanced significantly following Sul/Atorva treatment, suggesting the importance of cell cycle regulation in colon tumor inhibition. The tumor status of animals at treatment initiation dictates response to atorvastatin, sulindac and Sul/Atorva. The tumor inhibition observed with Sul/Atorva in tumor-bearing mice was greater than that achieved with either agent alone.

2018-08-31 | GSE81375 | GEO

Methylome Changes During the Progression of Colitis-accelerated Colon Cancer in Mouse and the Blockage by Curcumin

Project description:Inflammation is highly associated with colon carcinogenesis. Epigenetic mechanisms play an important role in the initiation and progression of colon cancer. Curcumin is a dietary cancer preventive phytochemical with promising effect in suppressing colitis-associated colon cancer (CAC) in azoxymethane (AOM) and dextran sulfate sodium (DSS) mouse model. In the present study, we confirmed the effect of curcumin in suppressing colon cancer. Using Agilent SureSelect Methyl-seq and RNA-seq, we obtained single-base methylation profile and transcriptome analyses of epithelial cells from control group, AOM and DSS induced group (AOM+DSS), and AOM and DSS induced plus curcumin treated group (AOM+DSS+Curcumin) in a 18 weeks long-term colon cancer mouse model. The average DNA methylation levels of the three groups are significantly different also. Based on differential methylation patterns of three groups, several pathways of genes were identified including IL-8 signaling, LPS-stimulated MAPK signaling and colorectal cancer metastasis signaling. Among these methylated pathways and genes, Tnf, an inflammatory gene stood out with decreased DNA CpG methylation in the AOM-DSS as compared to the control group and interestingly curcumin reversed the CpG methylation (validated by pyrosequencing). The functional role of DNA methylation of Tnf was confirmed by in vitro luciferase transcriptional activity assay. In addition, we found that a group of genes associated with the inflammatory responses and their methylation level was decreased in AOM+DSS group but restored in the curcumin treated group. Taken together, in this study, aberrant DNA CpG methylation of the inflammatory response was found in colitis-associated colon cancer and curcumin restored their CpG methlyation, which could potentially explain the inflammatory and cancer protective effects of curcumin. (Note this GEO/dataset is the DNA methyl-seq part of the study.)

2018-06-11 | GSE102645 | GEO

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