RECNAC Cancer Research Update

By Joseph Casciari, Ph.D.

The RECNAC project marked its 9th anniversary in February with a “Lunch and Lecture” presentation at The Center for the Improvement of Human Functioning International. Dr. Hugh D. Riordan, RECNAC Project Director, began the lecture by showing a clip from his original RECNAC project announcement in 1989. The project’s stated goal has been to learn why cancer develops and how it can be safely treated and prevented. The RECNAC project got its name from Zelma Barackman, a breast cancer patient who has survived fourteen years since using The Center’s approach to fight her disease.

… the key to finding successful treatments for cancer is knowing where to look …

According to Dr. Riordan, the key to finding successful treatments for cancer is knowing where to look, and being willing to search in unusual places. The RECNAC project has based its search on learning how nutrient deprivation affects cellular behavior and examining how host responses to cancer can be improved. Although the funding target for RECNAC has not been met, the RECNAC staff has made significant progress in finding new and safe cancer treatments.

Neil Riordan, RECNAC Project Manager, described an exciting new area of research based on training immune cells to fight cancer. Recent studies indicate that a specialized immune cell called the dendritic cell may be the key to mounting an effective immune response against cancer. Dendritic cells, named for the long branches protruding from their membranes, work by locating foreign antigens and presenting these antigens to T -cells. The T-cells then attack any cells that contain the antigen. Experimental studies show that cancer bearing animals given an infusion of dendritic cells ”trained” with tumor antigens have cure rates exceeding fifty percent.

Dendritic cell therapy has entered the clinical trial phase, and the RECNAC project is beginning work in this area. The clinical protocol involves isolating white blood cells from patients and treating them to induce dendritic cell growth. The dendritic cells are then ‘pulsed’ with antigens from tumor cells, given time to mature, and re-infused into the patient. Dendritic cell research at RECNAC started in the fall of 1997. The methodology for growing dendritic cells is now up and running, and RECNAC has received approval from The Center’s Institutional Review Board to begin clinical trials with dendritic cell therapy. In the meanwhile, research is ongoing to improve methods for dendritic cell growth, to discover new tumor antigens, and to optimize antigen ‘pulsing’ procedures.

In an effort to discover new anticancer agents, Dr. Xiao Long Meng has been isolating extracts from herbs and natural products and testing their effects on tumor growth. Dr. Meng described a promising new plant extract he has recently isolated and tested experimentally. Not only does this extract show toxicity against tumor cells in a dose dependent manner, but it also inhibits angiogenesis, the process whereby tumors induce new capillaries to grow toward them. Since angiogenesis provides tumors with the necessary blood supply for growth and metastasis, scientists have been looking for ways to inhibit it.

Dr. Meng’s new plant extract has recently been tested against three mouse tumor models at the Beijing Tumor Institute. In these models, an agent that inhibits tumor growth by thirty percent is considered promising. Dr. Meng’s plant extract inhibited tumor growth by fifty to seventy percent!

The RECNAC project has devoted considerable effort investigating the potential of high dose ascorbate therapy, and Dr. Joseph Casciari provided an update of RECNAC’s progress in this area Dr. Casciari tested ascorbate efficacy using colon cancer cells grown in three dimensions inside hollow fibers, and found that ascorbate induced a process called “apoptosis” in these tumor cells. Apoptosis is a form of programmed cell suicide that is critical for regulating normal tissue growth, but is thought to be defective in tumor cells.

RECNAC scientists also measured the ascorbate levels that are achieved during typical high dose infusions. Preliminary data indicate that, relative to healthy people, cancer patients and flu sufferers attain lower plasma ascorbate levels for a given dose. Perhaps the body’s demand for ascorbate increases with illness. Blood ascorbate levels during 60 gram infusions were high enough to kill prostate cancer cells in Petri dishes, but not high enough to kill the colon cancer cells grown inside hollow fibers. RECNAC scientists are testing combination therapies to increase ascorbate sensitivity. One novel approach has been shown to decrease the ascorbate dose required for tumor cell killing by a factor of four.

Dr. NinaMikirovadescribedoqgoing experiments to determine the effects of electric and magnetic fields (EMF) on cancer cells. Low frequency EMF is reported to affect several I aspects of cellular physiology, including DNA synthesis, immune cell response, and membrane signaling. However, reports from different laboratories vary in precisely what these effects are. Dr. Mikirova has developed an experimental system to treat cells with EMF fields in excess of 100 Gauss. Experiments thus far suggest that EMF can enhance the toxic effects of ascorbate against tumor cells. Dr. Mikirova is complementing these experiments with mathematical modeling of EMF effects on charged particles.

Finally, Paul Taylor described a new instrument acquired by RECNAC, the flow cytometer. A flow cytometer is a versatile particle counter that analyzes cells one at a time by hitting them with a laser. The flow cytometer can detect fluorescent markers that stain cells with certain properties. This allows, among other things, the detection of cells undergoing cell division or apoptosis. Populations of white blood cells can also be analyzed to determine the fraction of various specific cell types. The flow cytometer is a major weapon in the RECNAC arsenal.

The RECNAC Project is scheduled to continue until December 31, 1999.