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The purpose of this study is to determine if Resveratrol, a nutritional supplement, shows a beneficial effect in the cellular function of normal liver cells and diseased liver cells (cancer cells) in samples of liver tissue taken during elective liver surgery. Outcomes based on 3 measures will test the hypothesis that Resveratrol when used as a nutritional supplement will 1)improve metabolic function in liver cells, 2)reduce cellular growth and proliferation of cancer cells, 3)decrease inflammation in the liver.
Hepatic function will be assessed by standard laboratory techniques. Hepatocyte signaling pathway proteins will be measured using western blot analysis for protein expression and polymerase chain reaction for gene expression. Activation of signaling pathways in both native hepatocytes and carcinoma will be analyzed by multi-plex signal array. The effect on transcription factors that may be important in gene expression will be analyzed by transcription factor array. The effect of resveratrol in altering hepatocyte and cancer cell metabolism will be analyzed by proteomic analysis.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| resveratrol | Experimental | Resveratrol 1 g daily for 10 days |
|
| Placebo | Placebo Comparator | Placebo 1 pill daily for 10 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Resveratrol | Dietary Supplement | Resveratrol 1 gm po x 10 days prior to liver resection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Improved metabolic profile of liver cells | This outcome is a composite outcome and will be measured by assessing expression of multiple signaling proteins that are important in hepatic cell metabolism such as Akt, p38, Mitogen Activated Kinases, and Adenosine Monophosphate-activated Kinase (AMPK) and expression of gluconeogenic proteins such as Phosphoenolpyruvate carboxykinase (PEPCK). | 36 months |
| Measure | Description | Time Frame |
|---|---|---|
| Decreased cell growth and proliferation | This outcome is a composite outcome of cellular pathways important in cancer cell replication. This will be measured by the expression of genes and proteins that regulate hepatic cell growth/cell survival such as cyclin gene expression, expression of the tumor suppressor p53, and expression of apoptosis proteins Bcl-2 and Bcl-xl. | 36 months |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Brian G Harbrecht, MD | University of Louisville | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Louisville | Louisville | Kentucky | 40202 | United States |
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| ID | Term |
|---|---|
| D008113 | Liver Neoplasms |
| D006528 | Carcinoma, Hepatocellular |
| D015179 | Colorectal Neoplasms |
| ID | Term |
|---|---|
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077185 | Resveratrol |
| ID | Term |
|---|---|
| D000081225 | Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
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| Placebo | Drug | Placebo 1 pill daily X 10 days |
|
| Decreased hepatic inflammation | This outcome will be a composite outcome of pathways that regulate both cancer cell growth and inflammation. It will be measured by levels of genes and proteins for nitric oxide synthase, cytokines such as interleukin-6, and Nuclear Factor-kappa B signaling proteins. | 36 months |
| D008107 |
| Liver Diseases |
| D000230 | Adenocarcinoma |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D007414 | Intestinal Neoplasms |
| D005770 | Gastrointestinal Neoplasms |
| D005767 | Gastrointestinal Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D012002 | Rectal Diseases |
| D006841 |
| Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |