Cutting-Edge Strategies that may Enhance Survival
Part 1 /Adhesion Molecules
The following information is nothing short of amazing. The oncology industry has spent billions of dollars over the past 40 years “waging war against cancer.” However, even drugs touted as being great breakthroughs have rarely increased survival more than a few months for many late stage cancers. Evidence now clearly points to the fact that cancer surgery, despite offering great hope for many, is far too often itself a major cause of recurrent cancer, metastases, and decreased survival.1,2 The information in the following article, if utilized in a proactive and organized way by cancer patients, could dramatically enhance the published benefits regarding survival touted by pharmaceutical companies for even the most popular of chemotherapy drugs. This is evidence-based medicine at its finest, as it is founded on a growing body of studies published in the peer-reviewed, scientific literature. This approach could literally revolutionize the way cancer surgery is performed in the United States, and dramatically impact the lives thousands of cancer patients for the better.
It may be shocking to many, but cancer surgery itself has been shown to increase the risk of metastasis, or spread of the primary tumor. Why is this so important? For many cancers, it is the metastatic spread and not the primary tumor that proves to be fatal. The process of cancer growth and metastases is a complicated one. This is the first in a series of articles which will elucidate some of the critical processes and events in cancer growth and metastases and supply critical interventions that may protect against surgically-induced recurrence and metastasis at each step along the way. It is the author’s opinion that a properly executed preventive strategy could significantly and dramatically impact long term survival, quality of life, and improve chances for a cure.
There are several aspects of cancer-surgery that appear to both increase the chances of cancer spread and negatively impact survival. These mechanisms involve the areas of: cancer cell adhesion, induction of growth factors, immune suppression, new blood vessel growth, (angiogenesis) provoking dramatically increased levels of inflammatory chemicals, (cytokines) use of an open surgical technique vs. laparoscopic or minimally invasive surgery, employing general anesthesia and morphine-based pain relievers vs. paravertebral block (regional anesthesia) and the use of non-morphine-based pain relievers.
To begin with, the process of surgically removing a cancerous tumor may enhance the release of tumor cells into circulation via the blood or lymphatics, 3 Another side effect of surgery is to increase the production of adhesion molecules such as galectin-3, which enhances the ability of cancer cells that have broken away from the primary tumor to successfully form thriving colonies in distant parts of the body such as the brain and lungs.
It is unfortunate that the process of surgically removing a tumor may increase tumor cell adhesion. Why is this? Cancer cells must be able to adhere to the lining of blood vessels in order to begin the process of forming deadly, new colonies, distant from the primary tumor. This process involves attachment to cells lining the blood vessel walls via a receptor on the surface of the cancer cells called galectin-3. Galectin-3 is the “Velcro” if you will, facilitating the attachment and being critical to this attachment process. 4 Blocking this ability appears to significantly decrease the potential to form metastases. In an experiment performed to mimic the trauma induced by major surgery, researchers found that the binding of colon cancer cells to microvascular endothelial lung cells (tiny blood vessels lining the lungs) was increased by 250% vs. cancer cells not exposed to the surgical conditions. 4
Fortunately, researchers have investigated natural substances and found that a compound called modified citrus pectin (MCP) shows great promise in reducing the ability of these tumor cells to latch on to the walls of blood vessels, the first major step in establishing a viable cancer colony away from the primary tumor. The mechanism by which MCP performs this function is by binding to galectin-3. One experiment showed that MCP was able to block the adhesion of galectin-3 to the lining of blood vessels by an amazing 95%! 5 MCP has also been shown to directly inhibit cancer spread. The Journal of the National Cancer Institute published a study in which they found that prostate cancer spread to the lungs in rats was reduced by 43% in the group receiving MCP vs. the control group. Further, the size of the metastatic colonies was also reduced by 89% in the MCP group. 6 Human trials have also shown promise using MCP. One trial of 49 men with prostate cancer involved men who were given only two cycles of four weeks of MCP. This resulted in 22% of the men experiencing stabilization of their disease or improved quality of life. The authors concluded that “MCP seems to have positive impacts especially regarding clinical benefit and life quality for patients with far advanced solid tumor.” 7 Other promising studies with MCP have shown that it can induce up to 40 times the programmed cell death (apoptosis) in prostate cancer cell lines compared to un-treated prostate cancer cells.8,9
Another interesting and promising compound has also been studied for its ability to reduce cancer cell adhesion. It is an over-the-counter remedy called cimetidine, originally marketed as the antacid drug Tagamet®. Research has shown that cimetidine possesses significant anti-cancer activity by way of its ability to block the expression of another critical adhesion molecule called E-selectin on the surface of endothelial cells (cells that line the blood vessels). 10 In down-regulating E-selectin, cimetidine impacts another critical mechanism which rogue cancer cells use to latch onto the walls of blood vessels in order to start new satellite cancer colonies. Human studies have demonstrated cimetidine’s powerful anti-cancer properties. The British Journal of Cancer published one report where 64 colon cancer patients received chemotherapy with or without cimetidine. The duration of the study was one year. The control group (without cimetidine) had a 10-year survival rate of 49.8% vs. an almost 90% 10-year survival rate for the cimetidine group.11 One further astounding study demonstrated that three year survival in colon cancer patients was increased by 34% (from 59% to 93%) in patients given cimetidine for only one week at the time of surgery. 12
The exciting research presented thus far in the field of cancer cell adhesion molecules holds significant potential to exploit an early pathway utilized by cancer cells to form metastatic colonies which ultimately result in the demise of the majority of cancer patients. Both cimetidine and modified citrus pectin have compelling research demonstrating their safety and ability to favorably impact cancer patient’s quality of life and long-term survival.13 A reasonable program might involve taking at least 14 grams per day of MCP and 800 mg of cimetidine daily starting at least one week prior to cancer surgery and continuing for up to one year. However, nothing in this article should be construed as medical advice. It is recommended that anyone facing the challenge of cancer consult first with their medical doctor(s) before adopting or acting on any of the information contained in this article. Stay tuned for part II, Mitigating immune-suppression induced by surgery.
Jeffrey Mueller, M.D.
SaJune Institute for Restorative and Regenerative Medicine
- Vander Bij GJ, et al The peri-operative period is an underutilized window of therapeutic opportunity in patients with colorectal cancer. Ann Surg. 2009 May; 242(5): 727-34
- Ben-Eliyahu S, et al. Evidence that stress and surgical interventions promote tumor development by suppressing NK cell activity. Int J Cancer 1999 Mar 15; 80(6):880-8
- Yamaguchi K, et al. Significant detection of circulating cancer cells in the blood by reverse transcriptase-polymerase chain reaction during colorectal cancer resection. Ann Surg 2000 July;232(1):58-65
- Ten Kate M, et al. Influence of proinflammatory cytokines on the adhesion of human colon carcinoma cells to lung microvascular endothelium. Int J Cancer. 2004 Dec20;112(6): 943-50
- Nangia-Makker P. et al. Inhibition of human cancer cell growth and metastasis in nude mice by oral intake of modified citrus pectin. J Natl Cancer Inst. 2002 Dec 18;94(24):1854-62.
- Pienta KJ. et al. Inhibition of spontaneous metastasis in rate prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst. 1995 Mar 1;87(5):348-53. 7. Clin Med Oncol. 2007;1:73-80.
- Clin Med Oncol. 2007;1:73-80.
- Jackson CL et al. Pectin induces apoptosis in human prostate cells: correlation of apoptotic function with pectin structure. Glycobiology. 2007 Aug:17(8):805-19.
- Yan J et al. Pectasol C modified citrus pectin induces apoptosis and inhibition of proliferation in human and mouse androgen dependent and androgen independent prostate cancer cells. Integr Cancer Ther. 2010 may 11 (e-pub).
- Kawase, J. et al. Effect of cimetidine on E-selectin expression on vascular endothelium stimulated by anti-cancer drug. Gan To Kagaku Ryoho. 2007 Nov:34(12):1902-4.
- Matsumoto S. et al. Cimetidine increases survival of colorectal cancer patients with high levels of sialyl Lewis-X and sialyl Lewis-A epitope expression on tumour cells. Br J Cancer. 2002 Jan 21;86(2):159-60.
- Adams WJ et al. Short-course Cimetidine and survival with colorectal cancer. Lancet.
- Siegers S, Andresen JP, Keogh CP. Does Cimetidine improve prospects for cancer patients? A reappraisal of the evidence to date. Digestion 1999;60(5):415-421.