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The following article is published by the Brewer Science Library. Single copies of the article may be printed for the reader's personal research and study. Reproduction in any other manner, format or location is expressly prohibited.

                                     HYALURONIC ACID (HA)  &  CANCER
                                                     by Christina L. White

While doing a search for information about prostate cancer, a transcript was found of an article by Dr. Lance Morris, Use of Hyaluronic Acid to Enhance High Dose Intravenous Vitamin C in the Treatment of Cancer & Other Diseases, which he had presented in November of 2004, and can be found at:   (www.smartlifeforun.org/2004/11/newsletter.html).   He discussed several prostate cancer cases as well as a breast cancer case in which he utilized intravenous vitamin C at 75 grams along with 5 cc of a low molecular weight 1% hyaluronic acid solution and obtained positive results.    Dr. Morris is associated with the Wholistic Family Medicine Clinic (520-322-8122) in Tucson, Arizona. 

Early Cancer Work with HA by Dr. Falk:
The late Canadian oncologist, Dr. Rudy Falk, did some initial work with hyaluronic acid in the 1980’s, and demonstrated improved response and reduced side effects with his cancer patients by utilizing HA with low dose chemotherapy.  He also utilized vitamin C IV’s and NSAIDS.  His theory and innovative treatment of cancer is thoroughly described in the U.S. patent number                   5827834.   His original work is still carried on in Toronto, Canada, by one of his colleagues, Dr. Nasri, at the Nasri Chelation & Integrative Medicine clinic in Barrie, Ontario (705) 735-2354. 
A link to the clinic:  (www.nasrichelation.com/pages/contact_us.html).

Basics of Dr. Falk’s Use of HA with Cancer U.S. Patent #5827834:
As a progressive oncologist, Dr. Rudy Falk utilized several modalities with his cancer patients in order to gain more control over the rate of cancer progression, and also to modulate the side effects of any toxic therapy.  In investigating the body’s own immunological role in controlling cancer progression, the research pointed to the immune surveillance role of activated macrophages against the cancerous cells. 

Dr. Falk  noted in his patent the research demonstrating that in the cancer patient, although the macrophages were activated, they were not able to cause destruction to cancer cells; something was blocking them.  As he stated, when macrophages were removed from cancer patients, and then washed and cultured, they performed normally.  In his patent, he noted that in 1989 it was shown that the excessive levels of prostaglandins around the cancer cells, were what caused the macrophages to be unable to take action against the cancer cells.  In both test tube and animal studies, when the levels of prostaglandins were reduced by the use of non-steroidal anti-inflammatory (NSAIDS) drugs, such as indomethacin and naproxen, better control of cancer tissue growth could be effected.    The problem was that  NSAIDS produce significant side effects that patients were often unable to tolerate.     

The protocol he developed used hyaluronic acid as a carrier substance to more effectively reach the cancer cell’s  receptors (discussed further in this article), with NSAIDS, vitamin C, and small amounts of an appropriate chemotherapeutic agent.  He utilized intravenous, intratumor, intraperitoneal or intrapleural use of this therapy for his patients.   This protocol resulted in better penetration of the drugs into the tumor cells.  Hyaluronic acid helps to carry the agents further into the solid tumors increasing the amount of tumor destruction.  His patent application includes interesting case histories and  results of 40 patients with cancer or other health problems receiving his unique therapy.  

One of his case histories demonstrates how effective hyaluronic acid can be as a carrier to increase penetration of whatever is given with it.  The dieuretc, furosemide (Lasix), sometimes becomes ineffective at increasing urine output in patients that for various reasons have a poor kidney response.  One example shows that in the previous 12 hours, a 40 mg dose of Lasix only resulted in 400 ml of urine, whereas when the same dose of Lasix administered intravenously in hyaluronic acid, was able to produce 2,600 ml of urine in the same patient.   He states that HA with the Lasix can result in  a 3 to 5 fold increase in urine output.    

Cancer Cell Receptors CD44 & RHAMM and HA:
Hyaluronic acid is a negatively charged polysaccharide that is found throughout the human body, as it is part of the extracellular matrix, both at the cell surface and inside the cells.  It performs several functions in the body.  It serves as a scaffolding for other molecules, aiding in the structural integrity around the cells. It  also interacts directly with cell surface receptors, CD44 and RHAMM, and through them signals are given that affect intracellular activities.

The fact that CD44 and RHAMM receptors are expressed in greater numbers on cancer cells offers an avenue of transporting and targeting anti-cancer agents to tumors, metastatic lesions and lymphatic tissues.  Although Dr. Falk may have been one of the first doctors to recognize and utilize this capacity of hyaluronic acid, this function of HA is being utilized more and more today. 

This important receptor, CD44, comes in several forms, a short form that is found on normal cells and longer variations that occur on cancer cells.   The CD44 receptor is situated within the phospholipid membranes of the cells, with a part of it extending into the interior cell cytoplasm.  There it interacts with the intracellular machinery involved in cell movement, which can lead to cancer cells breaking off and creating metastases in other areas of the body.  Experimental research with the longer receptor form of CD44 demonstrated that when it was inserted into benign tumor cells, they became aggressive, metastasizing cancer cells.   The enzyme in the body that breaks down hyaluronic acid is hyaluronidase.   This enzyme also reduces the long form of CD44 into the short form, which is the normal and immobile form.  Research with mice given human breast cancer demonstrated significant  tumor shrinkage upon IV treatment with the hyaluronidase enzyme. 

HA Combined With Anti-Cancer Drugs:
It is very well known that chemotherapy treatments also come with significant toxicity to healthy tissue and sometimes severe side effects. In Australia,  Meditech Research Limited, has developed Hyaluronic Acid Chemotransport Technology (HyACTä).    This HyACTä technology has developed combinations of HA with established anti-cancer drugs, such as 5-fluorouracil, methotrexate, doxorubicin, and irinotecan.  In Phase I clinical trials these combinations have been shown to have increased efficacy and safety over the cancer drug itself.

Instilled  HA to Treat Bladder Cystitis:
A very purified form of hyaluronic acid, Bioniche’s Cystistat (www.bionche.com), is approved for distribution in Europe and Canada.  Cystistat is a liquid form of HA which is instilled directly into the bladder where it helps restore the glycosaminoglycan layer of the bladder tissue.  Bioniche has a patent on this treatment for Interstitial Cystitis; other conditions that could benefit would include: radiation cystitis, results of infection, urinary retention, or cancer.  Approximately 20% of men and women who receive either external beam radiation or intracavity radiation for pelvic malignancies, may experience distressing side effects called radiation cystitis, with symptoms of burning, pain, urinary urgency and frequency.  Utilization of Cystistat bladder infusions prior to radiation treatments can significantly reduce these side effects.  Cystistat is available to U.S. citizens from Canada.  To purchase Cystistat from Canada call 888-258-4199.  

Urine Test for Bladder Cancer Measures HA-Haase:
From the research lab of Vinata B. Lokeshwar, Ph.D., Associate Professor of Urology and Cell Biology and Anatomy, and her colleagues at the Miami University School of Medicine,  has come a patented urine test (HA-HAase) that is 90% accurate in detecting bladder cancer and can be used to monitor its recurrence.  The test can often pinpoint bladder cancer up to five months before a cystoscopy can identify it.  The urine test measures the concentrations of both hyaluronic acid (HA) and its degrading enzyme, hyaluronidase (HAase).  

HA-HAase Tumor Markers for Prostate Cancer:
Also from the research lab of Vinata B. Lokeshwar, Ph.D., has come a test that can help determine which prostate cancer is aggressive.  The research work from her lab demonstrated that HA and HAase are markers that can predict with 85% accuracy the aggressiveness of the tumor tissue recovered with radical surgery.   If the tissue shows high expression of HA and HAase, there is a 20-fold increased risk of progression for that prostate cancer patient.   This valuable information can help the physician and patient decide how aggressive their following treatment might be.   

Hyaluronic acid- Butyrate Esters in Cancer Research:
Butyrate is a dietary agent that can function as a weak histone deacetylase (HDAC) inhibitor in cancer cells and serve to disrupt the cell cycle and induce apoptosis by the downregulation of genes such as P21 and BAX.    A research project reported in the review paper, Hyaluronic Acid Butric Esters in Cancer Therapy,  Anti-Cancer Drugs, 2005, 16:373-379,  utilizing an esterified combination of them both found the combination to be 10-fold more effective than butric acid alone, in inhibiting the proliferation of several common human cancers.   In animal tests, the HA-But combination has shown positive results in inhibiting primary tumor growth as well as liver metastases, and prolonging survival time.

Links  to Other  Important Hyaluronic Acid Information:

Hyaluronic Acid:  Not With Cancer, Never With Aromatase Inhibitors.
This is an important newsletter article to read  from the  Denver Naturopathic Clinic.
This article can be found at www.denvernaturopathic@denvernaturopathic.com/news/hyal
This excellent article includes many research abstracts on various aspects of hyaluronic acid, the receptors and the enzyme hyaluronidase that degrades HA.

How to Live 100 Years Without Growing Old,  book by Bill Sardi.
Chapter eight has an excellent article on HA and cancer.  Bill Sardi also disagrees with some of the conclusions that are in the article from the Denver Naturopathic Clinic.   Here is the link to his rebuttal:   

Hyaluronan Promotes the Malignant Phenotype, mini review by Bryan P. Toole,   Glycobiology, 2002, Vol. 12, No. 3 37R-42R   Oxford University Press
FREE full text at:   www.glycob.oxforjournals.org/cgi/content/full/12/3/37R

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