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McAvoy, Researchers Investigate Link between Bacteria and Cancer of the Appendix


For many, the appendix is little more than a token of humankind’s evolutionary past, a vestigial organ that seems to contribute little to no function for the body.

Each year, however, the National Institutes of Health estimates that approximately one person per every 1 million people will develop what is known as pseudomyxoma peritonei (PMP), a very rare type of cancer that most often originates in the appendix as a small growth, known as a polyp.

This polyp eventually breaks through the wall of the appendix and disperses cancerous cells to the lining of the abdominal cavity, known as the peritoneum.

Unlike most cancers, PMP does not spread through the bloodstream or lymphatic system. Instead, a jellylike fluid known as mucin collects inside the abdomen, often but not always taking a long time to develop and cause symptoms.

PMP is rare and there exists a great need for understanding the factors that lead to PMP tumor growth and the spread of PMP to other organs in the body. In fact, the PMP Research Foundation estimates that most general practice doctors will see only one case of PMP each year, if any.

Knowing this, and driven by a personal connection to PMP, Professor Emeritus Thomas J. McAvoy (Department of Chemical and Biomolecular Engineering, Institute for Systems Research, Fischell Department of Bioengineering) set out in 2004 with Dr. Armando Sardi, Medical Director for the Institute for Cancer Care at Mercy, and the late Dr. Andre Dubois of the Uniformed Services University (USU) to learn more about a possible link between bacteria and PMP.

In 2008, the trio teamed up with other Mercy and USU researchers to publish a paper on bacterial involvement in PMP in the Annals of Surgical Oncology – just four years after McAvoy lost his beloved wife Jessie to the orphan disease.

In the paper, the research team noted that H. pylori, a bacterium that can cause stomach cancer and other bacteria, were found in PMP tumors. As such, McAvoy and his fellow researchers hypothesized that pre- and post-operative antibiotic treatment may enhance the efficacy of cytoreductive surgery to remove the mucinous tumor in the peritoneum, and heated intraperitoneal chemotherapy (HIPEC), a form of treatment performed after the surgery.

In 2009, Dubois and his lab director, Dr. Semino Mora, expanded the team’s research to study the β-catenin protein, and the team published results of the research in 2013 in Clinical Cancer Research.

“Normally, β-catenin resides in cell membranes and it helps cells adhere to one another,” McAvoy said. “When β-catenin migrates inside cells, it becomes easier for cells to metastasize, and increased levels of intracellular β-catenin are often an indicator of cancer.”

The β-catenin study compared 14 antibiotic treated patients to 34 not receiving antibiotics, and produced a comparison of bacterial densities in tumors from these two groups.

Incredibly, bacteria, including H. pylori, were detected in 83 percent of PMP tumors. In the more malignant form of PMP, patients treated with antibiotics had a significantly lower bacterial density and decreased β-catenin levels inside cells. Cell membrane β-catenin was significantly increased in all PMP patients receiving antibiotics, which indicates that the tendency for metastasis was decreased in patients who received antibiotics.

En masse, the research put forth by McAvoy and his colleagues offers hope that, in addition to cytoreductive surgery with HIPEC, PMP patients might benefit from a novel co-treatment with antibiotics.

“More recently we have studied the microbiome of PMP patients and published our results in the Orphanet Journal of Rare Diseases in 2013, been able to culture bacteria from tumors, and are initiating a study through the American Gut Project to assess any differences between the gut microbiomes of PMP patients and those of healthy people,” McAvoy said, adding that, while his research links bacteria and PMP, whether bacteria cause the disease or take advantage of it – and the potential benefits of pre- and post-operative antibiotics – have not yet been determined. The research is ongoing and additional PMP patients are being treated with antibiotics to assess their benefit. 

More information about McAvoy's personal journey to find a cure for PMP is featured in his latest book, Science Deepens Faith, available via Xulon Press.

 

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June 13, 2016


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