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May 16, 2002 |
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Freezing makes cancer cells prime targets for drug BERKELEY -- May 16, 2002 (Cancer Digest) -- The answer to improving the effectiveness of certain chemotherapy treatments for cancer may be in stopping the malignant cells cold. Researchers from the Institut Gustave-Roussy in France and the University of California, Berkeley found that freezing cancer cells in test tubes made them far more vulnerable to attack by bleomycin, a potent anti-cancer drug also known by the brand name Blenoxane®. It is used to treat several types of cancer, including cervical and uterine, head and neck, testicle and penile cancers, and certain types of lymphoma. Cryosurgery -- freezing cells to destroy them -- and bleomycin are approved treatments currently used separately for cancer patients. But the researchers led by Dr. Lluis M. Mir, senior researcher at the Institut Gustave-Roussy and lead author of the study, say that combining the two therapies may eventually lead to a powerful new form of targeted cancer treatment. The study was published in the May 14 issue of the British Journal of Cancer. "What we've found is a way to make cryosurgery more reliable," said Mir, who is also a senior scientist at the Centre National de la Recherche Scientifique (National Center for Scientific Research) in France. In the study, researchers froze melanoma cells in such a way as to mimic the conditions of cells on the outer rim of cryosurgically treated tissue where the temperature is often not cold enough to ensure cell death. During freezing, the cells were treated with bleomycin in trace concentrations several magnitudes smaller than what is used clinically for patients. The researchers then compared those cells to a control group of cells that were not treated with bleomycin. Cells in each group were thawed and cultured for 137 hours before researchers manually counted the resulting colonies of viable cells. Cells that were frozen without the bleomycin produced an average of 242 colonies. In sharp contrast, frozen cells treated with bleomycin produced no colonies, indicating a complete eradication of live cells. Even extremely low bleomycin concentrations had an effect, leaving only enough cells alive to produce an average of 13 colonies over four repetitions of the experiment. The combination of cryosurgery and bleomycin apparently compensates for each therapy's weakness. Contrary to almost all other anti-cancer drugs, bleomycin doesn't diffuse through the cell membrane. It must bind to specific receptors on the cell membrane to get in, and that is quite a limiting factor. The problem with cryosurgery is that freezing cells doesn't mean they will always freeze to death. Cells near the probe at the core of the ice mass reach a frosty minus 140 degrees Celsius (minus 220 Fahrenheit) and quickly die. But survival rates increase as temperatures warm from about minus 40 degrees C, often found on the outer edges of the freeze zone. By combining the two, the weakened membranes of the cells on the outer edge of the freeze zone apparently become vulnerable to the bleomycin, while neighboring, healthy cells outside the freeze zone keep their membranes intact protecting them from the bleomycin. Dr. Gary Onik a former University of California at San Francisco physician, who pioneered cryosurgery in 1981 with one of the study authors Dr. Boris Rubinisky of the University of California Berkely reviewed the present study before publication. He is optimistic about the finding. "The neat thing is that, this research really could have clinical applicability in a very rapid time frame," said Onik, currently the director of surgical imaging at Florida Hospital Celebration Health's Center for Surgical Advancement in Orlando, and one of the reviewers of the study. "However, it is critical that we first conduct animal model studies so that we better understand the parameters and risks involved in using cryochemotherapy treatment in humans," he cautioned. |
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