Surgical Oncology Laboratory

In Focus: Mechanisms and Preventive Approaches to Carcinogenesis Robert C. Martin, MD Associate Professor Director, Division of Surgical Oncology

A Radical Idea
Could a natural boost help prevent cancers of the esophagus and liver? Anti-oxidants protect the body from the oxidative stress of free radicals, which damage cells by reacting with DNA or the cell membrane—contributing to the development of cancer. Natural substances, as well as those that mimic the effects of a key anti-oxidant in the body, may be an answer to prevention of these two types of cancer.

Esophageal Adenocarcinoma
The local micro-environment within the esophageal mucosa is responsible for the development of cancer. It is believed that gastro-esophageal reflux disease (GERD) is an underlying trigger for the development of Barrett’s esophagus and esophageal adenocarcinoma.

The Laboratory's researchers are investigating the anti-oxidative defense system, in particular the antioxidant enzyme manganese superoxide dismutase (MnSOD), and how its function may be altered during the transition from reflux esophagitis to Barrett’s esophagus and esophageal adenocarcinoma. They are also testing nutritional supplements that mimic MnSOD to determine if they are effective in preventing esophageal cancer.

In addition, certain phytochemicals found in foods that have potent anti-oxidant properties, including—resveratrol, curcumin and anthocyanin—are under investigation to determine if they have protective effects against esophageal adenocarcinoma.

Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) is one of the most frequently occurring cancers in the world. Risk factors include viruses, chemicals, and hormones. Evidence indicates that liver cirrhosis plays a major role in the carcinogenesis of HCC.

Our laboratory is investigating the precancerous condition and mechanisms of transition from normal hepatocyte to HCC. Specifically, we hope to determine whether the presence of nodules containing proliferating hepatocytes and irregular proliferation associated with reactive oxygen species (ROS) may produce genetic cellular abnormalities that lead to the development of HCC. To test this hypothesis, we are using siRNA to silence particular anti-oxidants. We also are using phytochemicals with potent anti-oxidant properties such as curcumin to explore the potential efficacy of this therapeutic strategy.

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