Download Essiac - CAM

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Neuropsychopharmacology wikipedia , lookup

Prescription costs wikipedia , lookup

Discovery and development of antiandrogens wikipedia , lookup

Tamoxifen wikipedia , lookup

Psychopharmacology wikipedia , lookup

Pharmacogenomics wikipedia , lookup

Bad Pharma wikipedia , lookup

Bilastine wikipedia , lookup

Bevacizumab wikipedia , lookup

Pharmacognosy wikipedia , lookup

Transcript
Concerted Action for Complementary and Alternative Medicine Assessment in the Cancer Field (CAM-Cancer) www.cam-cancer.org
Project initiated under the European Commission 5th Framework Program "Quality of Life", now hosted by the National Information Center for
Complementary and Alternative Medicine in Tromsø, Norway.
Scientific Co-ordinator Barbara Wider [email protected].
Written by Katja Boehm and the CAM-Cancer Consortium.
Updated April 29, 2016
Essiac
Abstract and key points
Essiac is a herbal mixture usually
administered as tea. It is promoted
mostly via the internet as an alternative
cancer cure.
Essiac is a herbal mixture mainly administered as
tea.
There is no evidence for Essiac as an effective and
safe cancer treatment.
There is no evidence from clinical trials
to indicate that it is effective. No clinical
trial has been carried out to assess its efficacy and the only published uncontrolled clinical investigation did
not suggest that Essiac has an effect on tumour burden.
The safety profile of Essiac is largely unknown but some of its ingredients are associated with possibly
considerable adverse effects. Patients are advised not to use any other cancer treatments including chemo- or
radiotherapy.
What is it?
Scientific name / brand name / common name
Essiac tea has been used for over 70 years as a remedy for the adverse effects caused by conventional cancer
treatments and supposedly for curing cancer itself. The name ‘Essiac’ was created by the Canadian nurse
Renée M. Caisse (‘Essiac’ is ‘Caisse’ spelled backwards)1-3. Other Essiac products are known as
Flor-Essence®.
Ingredients
The four herbs contained in Essiac® are:
• Burdock root (Arctium lappa L.),
• Indian rhubarb root (Rheum officinale L.),
• Sorrel (Rumex acetosa L.)
• Slippery elm bark (Ulmus rubra/fulva Muhl.)
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
1/9
A modified Essiac product (Flor-Essence®) also includes the following four additional herbs:
• Watercress (Nasturtium officinale L.),
• Blessed thistle (Centaurea = Cnicus benedictus L.),
• Red clover (Trifolium pratense L.) and
• Kelp (Laminaria digitata).
History / providers
According to Renée Caisse, an English miner’s wife had received the recipe for Essiac from a Native
Ojibwa Indian medicine man, and had cured her breast cancer with this treatment. Renée Caisse, who
worked at the Bracebridge Cancer Clinic in Ontario, Canada from 1935 to 1941, treated cancer patients with
Essiac herbal tea for 50 years.
In 1938, concerns about the use of Essiac were raised, after evidence of one reported death and one report of
toxicity after Essiac tea injections emerged4,5. In 1941, the Bracebridge Cancer Clinic was closed following
a request by the Canadian authorities. Between 1959 and 1978 Caisse worked with Dr Charles Armao
Brusch, director of the Brusch Medical Clinic in Cambridge, Massachusetts, in the US, to modify the
original recipe and promote the use of Essiac. After carrying out some laboratory studies on mice, four
further herbs were added to the recipe (see above) to improve the healing action and taste of Essiac. In 1977
Mrs Caisse sold the original Essiac recipe to Resperin Corporation Ltd of Toronto, Canada.
In 1982 the Resperin Corporation Ltd carried out some poorly designed trials in which physicians using the
product were asked to submit case reports. The Canadian Department of National Health and Welfare
terminated the tests, claiming that Resperin had conducted a poorly conceived and executed investigation.
Health Canada concluded that the evidence was unconvincing and that there was no scientific evidence to
support claims that Essiac could cure cancer6. However, under the Canadian Emergency Drug Release
Programme, Essiac could be obtained on physician’s request. In 1995 the Essiac formula and its trademark
were purchased from Resperin Corporation Ltd by David Dobbie. Thus, Essiac® Products Inc of New
Brunswick became the manufacturer of Essiac®. Another Canadian product, Flor-Essence®, is
manufactured in British Columbia, where Charles Armao Brusch is involved in using the eight herbs of the
modified Essiac formula. Nowadays, more than 40 different formulas of Essiac are available globally.
Claims of efficacy / mechanisms of action / alleged indication
Renée Caisse documents her view of how Essiac affects the cancer process as follows: after enlarging and
hardening of the tumour following the first few treatments, tumour softens and, if the tumour was located
near an exterior route, the patient discharges large amounts of pus and fleshy material. She believed that
somehow Essiac would cause cancerous cells to retreat to the site of the original tumour where they would
then shrink and vanish.
Charles A Brusch claimed that Essiac works by identifying toxins, gathering them, breaking them down and
discharging them. He also suggested that in an unpublished double-blinded study carried out by his institute,
positive results were observed including pain cessation, increased appetite, improved sleep, well-being and
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
2/9
energy, decreased depression, anxiety and fear and a decrease in nodular masses.
The explanations put forward for a mechanism of the therapy are not supported by good evidence, nor are
they deemed a possible and sufficient explanation by current scientific standards.
Application and dosage
The tea is usually taken 1-3 times before meals to minimise possible adverse effects such as nausea,
vomiting and diarrhoea. Initially, Caisse administered one of the herbs by injection and gave the others as
tea. Nowadays, most products are in tea form but other products also exist in the form of drops, capsules,
liquids and dry versions. The patient is supposed to boil the mixture and then drink the tea. The patient
information also advises that no other treatment, including chemotherapy and radiotherapy, should be used
while taking Essiac.
Prevalence of use
In 1982 when Canadian health officials conducted a retrospective review of Canadian patients treated with
Essiac they found that about 150 physicians in Canada had at that stage reportedly requested supplies of
Essiac on behalf of their cancer patients7. In a Canadian survey from 2000 among women with breast cancer
15% reported using Essiac (ResperinTM, Canada Limited)8. Two further surveys were carried out in the
USA and targeted specifically at Flor-Essence® users in order to quantify its use, it was found that among
the 5051 respondents 22% were diagnosed with breast cancer9,10. Finally, in a survey at the Royal Marsden
Hospital in London, UK 318 cancer patients were asked about their use of Essiac and 6% reported using
Essiac11.
Legal issues
Essiac cannot be marketed as a drug because it has no licence. It is therefore usually sold as a nutritional
supplement. In Canada, Essiac is currently unapproved for marketing and cannot be used in clinical trials
without a valid preclinical new drug submission. However, the Canadian government allows Essiac to be
manufactured and sold. Manufacturers are not allowed to make any medical claims, instead Essiac is
promoted as a health-enhancing herbal tea. Patients who wish to obtain Essiac must ask their physician to
make a request to the Canadian Bureau of Human Prescription Drugs, which relays the order to the company
and the company then ships it directly to the patient.
Costs
Essiac products vary in price from €4.15 to hundreds of Euros per month for pre-made bottled blends. A
pre-fabricated Essiac tea can range from €15.00 to €24.00 per ounce bottle. A higher price does not
necessarily indicate higher quality of the product. In 2001, the annual US Essiac sales were estimated to
exceed US$ 8 million9.
Does it work?
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
3/9
Does it work?
Reviews
Three reviews exist in the peer-reviewed literature1,2,12, which did not identify a single published clinical
trial. The first review, by Kaegi et al.1 discusses the history and safety of Essiac along with laboratory and
clinical evidence. The second review by Boon et al.2 reviews the efficacy and safety of various botanical
medicines (including Essiac). The third is a systematic review carried out in the USA by researchers at
Natural Standard (an international multidisciplinary collaboration including contributors from more than 100
academic institutions) showed a lack of high-quality clinical trials to substantiate any of Essiac's traditional
uses12. The results are inconclusive despite indications from preclinical, animal and laboratory data
suggesting possible positive effects caused by Essiac application.
Controlled trials
No controlled studies are available.
Epidemiological studies
In a retrospective cohort study of Essiac to ascertain its effects in women with breast cancer in Canada, 510
women with a positive breast cancer pathology report who were diagnosed between 2001 and 2003
responded to a mail survey13. The survey packet included a) the Functional Assessment of Cancer Therapy
Breast Cancer Version (FACT-B), b) the Profile of Mood States (POMS), c) the Yale Social Support Index
(YALE), d) Patterns of use of Essiac and e) prevalence of general use of complementary and alternative
medicine. Overall, 8.1% of the surveyed women were using Essiac. Results showed that there were di
fferences on one of the subscales regarding health-related quality of life (physical well-being) as assessed by
the FACT-B scale (p<0.02) between Essiac users and non-users for which Essiac users seemed to score
better. However, on all other subscales, women who reported Essiac use consistently had higher scores
compared to non-users, meaning that scores for health-related quality of life and mood were generally worse
in Essiac users. Furthermore, Essiac seemed to have a negative effect on users as those reported scores
indicating a higher burden due to their disease. Dose, frequency of use and brand of Essiac product did not
affect disease-specific QoL or various mood states on the POMS. However, the authors of the survey put
forward the likely explanation that Essiac use is a marker of physical distress. Only two adverse events were
reported in this survey, involving mild gastrointestinal upset and an unpleasant taste.
Case series/reports
A Canadian study collected case reports submitted voluntarily by physicians. This case series included 86
patients with advanced cancers who had been treated with Essiac7. Forty-seven patients received “no
benefits”, eight of the reports were impossible to evaluate, 17 patients died, one patient experienced
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
4/9
‘subjective improvement’, five required fewer analgesics, four had an ‘objective response’, and four were in
‘stable condition’. All of the patients also received conventional treatment, which could have explained their
improvement.
Pre-clinical studies
Essiac was tested in a mouse sarcoma model in the US by the Memorial Sloan Kettering Laboratories, New
York, in 1959 and again from 1973 to 197614,15. Some unpublished preliminary reports suggested some
evidence of biological activity. The results of six immunotherapy tests and two chemotherapy tests of Essiac
samples as tested on the mouse sarcoma model, showed no activity.
An in-vitro study comparing Essiac® and Flor-Essence® in human breast cancer cells found that both of the
teas demonstrated antiproliferative and differentiation inducing properties, but this effect was only observed
at high concentrations (1/10 and 1/100)3.
Most of Essiac’s identifiable components have shown anti-cancer properties individually16-24.
In a Canadian animal lab study Essiac was administered orally to rats25. The administration demonstrated a
modest gastric protective effect. In 2006 a U.S. study wanted to assess the effect of Flor-Essence® and
Essiac® on cell proliferation. Herbal tonics were tested in various types of cancer cells isolated from human
breast tumors26. It was found that Flor-Essence® and Essiac® herbal tonics can stimulate the growth of
human breast cancer cells in vitro through estrogen receptors mediated as well as estrogen receptors
independent mechanisms of action.
A Canadian-Australian research team carried out another in vitro analysis of Essiac® by measuring its
activity27. The in vitro analysis showed significant antioxidant and immuno-modulatory properties as well
as neoplastic, cell specific cytotoxicity,.
Another Canadian research team evaluated the anti-proliferative effects of Essiac TM on in vitro and in vivo
models of prostate cancer compared to Paclitaxel. The investigations showed no marked anti-proliferative
effect28.
Is it safe?
There is no literature regarding the safety of Essiac. The above review from the Natural Standard
Collaboration notes that there is a lack of safety data for Essiac and the other preparations that are marketed
under the exact formula12. However, it cannot be assumed that Essiac is safe as it is a product with an
unknown safety profile particularly with regards to use during pregnancy and lactation and concomitant use
with other drugs.
Patients are also at risk as they are advised that no other treatment, including chemotherapy and
radiotherapy, should be used while taking Essiac.
Adverse effects associated with its use have not been reported. The constituent herbs may cause allergic
dermatitis and have a laxative effect29,30.
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
5/9
Contraindications
None currently known
Precautions/warnings
None currently known.
Adverse effects and interactions
The following information regarding safety, adverse effects and interactions is available from Natural
Medicines Comprehensive Database 31 for the individual plants Essiac contains:
Burdock root (Arctium lappa L.) Orally, burdock can cause an allergic reaction. Rarely, it has caused
anaphylaxis32. Theoretically, taking burdock with anticoagulant or antiplatelet drugs might increase the risk
of bleeding due to decreased platelet aggregation.
Indian rhubarb root (Rheum palmatum) Orally, rhubarb can cause cramp-like or spasmodic gastrointestinal
discomfort, watery diarrhoea, and uterine contractions; there is also one report of anaphylaxis with
short-term use33. Chronic use or abuse of rhubarb can cause electrolyte loss (especially potassium),
hyperaldosteronism, accelerated bone deterioration, albuminuria, hematuria, dehydration, inhibition of
gastric motility, pseudomelanosis coli (pigment spots in intestinal mucosa), arrhythmias, muscular
weakness, nephropathies, and edema34.
Sorrel (Rumex acetosa L.). Orally, excessive amounts of sorrel can cause diarrhoea, nausea, polyuria,
dermatitis and gastrointestinal symptoms. Theoretically, concomitant oral administration may cause
precipitation of some drugs due to the high tannin content of sorrel.35.
Slippery elm bark (Ulmus rubra Muhl.) Orally, the whole bark is an abortifacient36. Topically, slippery elm
extracts can cause contact dermatitis and the pollen is an allergen. In theory, the consumption of slippery
elm bark when taken with other drugs may slow the absorption and reduce serum levels of orally
administered drugs due to mucilage content35.
Watercress (Nasturtium officinale). Orally, large amounts of watercress can cause gastrointestinal irritation
33. Theoretically, excessive or prolonged use might cause kidney damage35. Consuming large amounts of
watercress with high vitamin K content might theoretically antagonize the anticoagulant effects of warfarin
37.
Blessed thistle (Centaurea = Cnicus benedictus). When administered orally and used in doses greater than
5g/cup of tea, it can cause stomach irritation and vomiting34.
Red clover (Trifolium pratense). The oral administration can cause rash-like reactions, myalgia, headache,
nausea, and vaginal spotting38. Concomitant use with drugs that have constituents that might affect platelet
aggregation could theoretically increase the risk of bleeding in some people. Concomitant use of large
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
6/9
amounts of red clover can theoretically increase the anticoagulant effects and bleeding risk of these drugs
due to its coumarin content37. There is some concern that red clover might interfere with the effects of
tamoxifen because of its potential estrogenic effects38.
Kelp (Laminaria digitata). Orally, kelp can induce or exacerbate hyperthyroidism39,40. The iodine in kelp
can cause idiosyncratic reactions. Prolonged high intake of dietary iodine is associated with goitre and an
increased risk of thyroid cancer41. Kelp seems to have anticoagulant effects and therefore, theoretically,
taking kelp with antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding42.
Quality issues
The quality of the mixture depends on the quality of each individual ingredient used in preparing the
mixture.
Citation
Katja Boehm, CAM-Cancer Consortium. Essiac [online document].
http://www.cam-cancer.org/The-Summaries/Herbal-products/Essiac. April 29, 2016.
Document history
Assessed as up to date in April 2016 by Barbara Wider.
Assessed as up to date in January 2015 by Barbara Wider.
Assessed as up to date in February 2013 by Katja Boehm.
Fully revised and updated in December 2011 by Katja Boehm.
Fully revised and updated in August 2009 by Katja Boehm.
Summary first published in May 2005, authored by Katja Boehm and Edzard Ernst.
References
1. Kaegi E. Unconventional therapies for cancer: 1. Essiac. The Task Force on Alternative Therapies of
the Canadian Breast Cancer Research Initiative. CMAJ 1998;158:897-902.
2. Boon H, Wong J. Botanical medicine and cancer: a review of the safety and efficacy. Expert Opin
Pharmacother 2004;5:2485-501.
3. Tai J, Cheung S, Wong S, Lowe C. In vitro comparison of Essiac and Flor-Essence on human tumor
cell lines. Oncol Rep 2004;11:471-6.
4. Thomas R. The Essiac report: The True Story of a Canadian Herbal Cancer Remedy and of the
Thousands of Lives it Continues to Save, 3rd ed. Los Angeles: Alternative Treatment Information
Networks, 1993.
5. Meehan D, Agar J. Doctor’s license suspended; some patients still support him. The Grand Rapids
Press, April 18th, 1997:12.
6. http://www.cancer.gov/cancertopics/pdq/cam/essiac/patient/page2 (accessed 6 February 2013)
7. Henderson IWD. Director, Bureau of Human Prescription Drugs, Health Protection Branch, Health
and Welfare Canada, Vanier, Ontario. Letter to J.W. Meakin. Executive Director, Ontario Cancer
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
7/9
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
Treatment and Research Foundation, Toronto, Ontario, November 19th 1982.
Boon H. Use of complementary / alternative medicine by breast cancer survivors in Ontario:
Prevalence and perceptions. J Clin Oncol 2000;18:2515 – 2521.
Low Dog T. Traditional and alternative therapies for breast cancer. Altern Ther Health Med 2001;
7:36-47.
Tamayo C, Richardson M. Presentation at 36th Annual Drug Information Association Meeting.
Baltimore, MD, June 17-21, 1999.
Morita H, et al. Cytotoxic and mutagenic effects of emodin on cultured mouse carcinoma FM3A cells.
Mutat Res 1988;204:329-32.
Ulbricht C, Weissner W, Hashmi S, Rae Abrams T, Dacey C, Giese N, Hammerness P, Hackman DA,
Kim J, Nealon A, Voloshin R. Essiac: systematic review by the natural standard research
collaboration. J Soc Integr Oncol 2009;7(2):73-80.
Zick SM, Sen A, Feng Y, Green J, Olatunde S, Boon H. Trial of Essiac to ascertain its effect in
women with breast cancer (TEA-BC). Journal of Alternative and Complementary Medicine
2006;12(10):971-80.
Hutchinson DJ. Experimental Chemotherapy, Memorial Sloan-Kettering Cancer Center, Rye, N,
personal communication, September 26, 1988 and March 1989.
Glun GL. Essiac. Nature’s cure for cancer. Wildfire 1991:6:48-55.
Foldeak S, Dombradi GA. Tumor-Growth Inhibiting Substances of Plant Origin. I. Isolation of the
Active Principle of Arctium lappa. Acta Phys Chem 1964;10:91- 93.
Dombradi CA, Foldeak S. Screening Report on the Antitumor Activity of Purified Arctium Lappa
Extracts. Tumori 1966;52:173.
Itokawa H, Watanabe K, Mihara K. Screening Test for Antitumor Activity of Crude Drugs (2).
Shoyakugaku Zasshi 1982;36:145-9.
Woo WS, Lee EB, Chang I. Biological Evaluation of Korean Medicinal Plants. II. Yakhak Hoe Chi
1977;21:177-183.
Morita K, Kada T, Namiki M. A desmutagenic factor isolated from burdock (Arctium lappa Linne).
Mutat Res 1984;129:25-31.
US Congress, Office of Technology Assessment: Unconventional Cancer Treatments. Washington,
DC: U.S. Government Printing Office, 1990. OTA-H-405, pp 71-5.
Belkin M, Fitzgerald DB. Tumor-Damaging Capacity of Plant Materials. 1. Plants Used as Cathartics.
J Natl Cancer Inst 1952;13:139-155.
Kupchan SM, Karim A. Tumor inhibitors. 114. Aloe emodin: antileukemic principle isolated from
Rhamnus frangula L. Lloydia 1976;39:223-4.
Pettit GR, Blazer RM, Reierson DA. Antineoplastic agents. 51. The yellow jacket Vespula
pensylvanica Lloydia 1977;40(3):247-52.
Leonard BJ, Kennedy DA, Cheng FC, Chang KK, Seely D, Mills E: An in vivo analysis of the herbal
compound essiac. Anticancer Res 2006; 26(4B):3057-3063.
Kulp KS, Montgomery JL, Nelson DO, Cutter B, Latham ER, Shattuck DL, Klotz DM, Bennett LM.
Essiac and Flor-Essence herbal tonics stimulate the in vitro growth of human breast cancer cells.
Breast Cancer Res Treat 2006; 98(3):249-59.
Seely D, Kennedy DA, Myers SP, Cheras PA, Lin D, Li R, Cattley T, Brent PA, Mills E, Leonard BJ:
In vitro analysis of the herbal compound Essiac. Anticancer Res 2007; 27(6B):3875-3882.
28.
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
8/9
28. Eberding A, Madera C, Xie S, Wood CA, Brown PN, Guns ES: Evaluation of the antiproliferative
effects of Essiac on in vitro and in vivo models of prostate cancer compared to paclitaxel. Nutr Cancer
2007; 58(2):188-196.
29. Rodriguez P, Blanco J, Juste S, et al. Allergic contact dermatitis due to burdock (Arctium lappa).
Contact Dermatitis 1995;33:134-5.
30. Schulz V, Hansel R, Tyler VE. Rational Phytotherapy: A Physician's Guide to Herbal Medicine. Terry
C. Telger, transl. 3rd ed. Berlin, GER: Springer, 1998.
31. Natural Medicines Comprehensive Database http://www.naturaldatabase.com/ (accessed 6 February
2013).
32. Sasaki Y, Kimura Y, Tsunoda T, Tagami H. Anaphylaxis due to burdock. Int J Dermatol
2003;42:472-3.
33. Gruenwald J, Brendler T, Jaenicke C. PDR for Herbal Medicines. 1st ed. Montvale, NJ: Medical
Economics Company, Inc., 1998.
34. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical
Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
35. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical
Publications, 1998.
36. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals.
London, UK: The Pharmaceutical Press, 1996.
37. Bolton-Smith C, Price RJ, Fenton ST, et al. Compilation of a provisional UK database for the
phylloquinone (vitamin K1) content of foods. Br J Nutr 2000;83:389-99.
38. Tice J, Cummings SR, Ettinger B, et al. Few adverse effects of two red clover extracts rich in
phytoestrogens: a multicenter, placebo-controlled trial. Alt Ther Health Med 2001;7:S33.
39. Nelsen J, Barrette E, Tsouronix C, et al. Red clover (Trifolium pratense) monograph: A clinical
decision support tool. J Herbal Pharmacotherapy 2002;2:49-72.
40. This P, De La Rochefordiere A, Clough K, et al. Phytoestrogens after breast cancer. Endocr Relat
Cancer 2001;8:129-34.
41. Baker DH. Iodine toxicity and its amelioration. Exp Biol Med (Maywood) 2004;229:473-8.
42. Phaneuf D, Cote I, Dumas P, et al. Evaluation of the contamination of marine algae (Seaweed) from
the St. Lawrence River and likely to be consumed by humans. Environ Res 1999;80:S175-S182.
Legal notice
The present documentation has been compiled by the CAM-CANCER Project with all due care and expert knowledge.
However, the CAM-CANCER Project provides no assurance, guarantee or promise with regard to the correctness,
accuracy, up-to-date status or completeness of the information it contains. This information is designed for health
professionals. Readers are strongly advised to discuss the information with their physician. Accordingly, the
CAM-CANCER Project shall not be liable for damage or loss caused because anyone relies on the information.
Please visit the CAM-Cancer website for more information about the project:
www.cam-cancer.org
Published with Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 Unported License
www.cam-cancer.org
9/9