Resveratrol and Human Hepatocyte Function in Cancer

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Resveratrol and Human Hepatocyte Function in Cancer

Conditions
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Liver Cancer

Intervention / Treatment
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* Dietary Supplement: Resveratrol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing elective liver resection for liver cancer Exclusion Criteria: Inability to speak or read English Sclerosing cholangitis, hemochromatosis, hepatic encephalopathy, acute hepatic failure History of daily alcohol intake Presence of human immunodeficiency virus Presence of significant renal dysfunction as defined by baseline serum creatinine > 2.0 mg/dl or need/impending need for chronic dialysis therapy Known allergy to the study medication Pregnancy, lactating women, women contemplating pregnancy during the study period

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: resveratrol<br>Resveratrol 1 g daily for 10 days | Dietary Supplement: Resveratrol<br>* Resveratrol 1 gm po x 10 days prior to liver resection<br>* Other names: Biotivia;|
| Placebo Comparator: Placebo<br>Placebo 1 pill daily for 10 days | Drug: Placebo<br>* Placebo 1 pill daily X 10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatocellular carcinoma, Metastatic colorectal cancer, Metabolism, Hepatic function