Dana Myatt, N.M.D. and Mark Ziemann, R.N.
Some types of cancer are consistently responsive to conventional medical treatment, especially those amenable to surgical intervention when diagnosed early. Cytotoxic therapy is helpful in selected instances. For most cancers, especially those advanced beyond Stage I or II, conventional treatments that evoke durable remissions are elusive and inconsistent. In many instances, cytotoxic and radiation therapies end a patient’s life sooner than the natural course of the disease would be expected to.
Alternative cancer therapies, while typically gentler and less inherently dangerous, have also proven inconsistent for evoking durable remissions. However, instances can be found where durable remissions and event apparent cure have been obtained by unconventional and alternative treatments used as stand-alone therapy. When used in conjunction with conventional treatments, alternative therapies can sometimes potentiate the positive effects of conventional therapy, mitigate the negative effects, or both.
The questions we will examine in this presentation include:
I.) Which alternative treatments are most effective as the sole treatment for malignancy and when should they be used?
II.) Which alternative treatments are most effective as adjuncts to conventional therapy?
III.) Which alternative treatments may be contraindicated for adjunct cancer therapy?
A careful review of the medical literature reveals that there are in fact specific modes of action to explain when and why alternative treatments are effective and when such treatments fail.
Cancer Cell Characteristics: Understanding the Enemy
Developing a cohesive and effective treatment strategy requires an understanding of the behavior and biology of cancer cells. Although various cancer types display unique behaviors, there are a number of characteristics common to all solid tissue malignancies:
1. Altered interactions with neighboring cells. Unlike normal cells whose division stops when neighboring cells are encountered, cancer cells continue to multiply with uncontrolled growth. This trait is known as lack of contact inhibition.
Normal cells require a solid substrate (basement membrane) upon which to grow. This is known as anchorage-dependent growth. Cancer cells are anchorage-independent, growing in circumstances where they are deprived of substrate.
2. Altered cellular metabolism. Cancer cells demonstrate a greatly increased rate of glucose transport. Anaerobic glycolysis is the predominant energy pathway of cancer cells, even in the presence of adequate oxygen. This may partly explain the large amount of metabolic acids produced by cancer cells.
Tumor cells have reduced growth requirements and will proliferate in culture media (less than 1% serum) that halt cell growth and division of normal cells.
3. Vascularization. Tumor cells secrete angiogenic growth factors which cause non-neoplastic blood vessels to grow from surrounding normal tissue. Research indicates that associated fibrin deposits many be necessary for angiogenesis. (1,2)
4. Invasion and metastasis. Multiple characteristics allow for local invasion and distant metastasis.
Cancer cells often secrete enzymes including collagenase, heparinase and stromolysin which are capable of degrading basement membrane and allowing invasion of tumor into adjacent tissues and general circulation.
Inflammation is caused by cellular substances, high acid cellular waste, and tumor pressure on adjacent normal tissue which produces histamine, leukotrienes and prostaglandins of the 2 series, increasing capillary permeability.
Anchorage independence (discussed above) allows cancer cells to travel through the blood stream without substrate. Normal cells do not have this ability. Once a clump of cancerous sells has made its way into general circulation, aggregates of platelets and/or fibrin encasement may serve as protection from the immune system.
Cancer cells have affinity for metastasis to certain and predictable locations not related to obvious blood flow patterns. Unidentified tissue chemotactic factors or lectin binding sites may account for this attraction. (3)
5. Escape from immune surveillance. Carcinogenic burden may simply overwhelm available immune surveillance, especially in the immunocompromised host.
Many cancer patients have apparently intact immune systems, however, and it is felt that cancer cells may secrete substances which circumvent the host’s immune response. Such immune-eluding substances include prostaglandins and other inflammatory substances. Fibrin and platelet aggregation may also serve to assist in protection from host immune response.
Tumor cells also appear to escape host immunity by down-regulation of Human Leukocytic Antigen (HLA) expression. HLA assists lymphocyte recognition of target cells.
Causes of Cancer
Understanding the causes of a particular cancer gives valuable clues to vulnerabilities and points of attack. Immune system dysfunction has long been considered a primary cause and point of treatment in alternative cancer treatment. However, there is significant evidence to suggest that immune dysfunction is only one of a number of causative factors and certainly NOT the most important one.
It appears that very few cancers have a single cause or “initiator.” Instead, most cancers may begin as a series of combination of events that lead to mutation. Tumor initiation begins when DNA in a cell or population of cells is damaged by exposure to exogenous or endogenous carcinogens. This alone is not sufficient to give rise to cancer. Damage at this point can be repaired. If DNA damage is not repaired or damaged cells eliminated, and if the microenvironment of the damaged calls are suitable to contribute to cell growth, then the process continues to the “promotion” phase. (48,49,50,51,52)
Known initiators of cancer include:
1. Genetic factors. A number of genetic factors may play a role in susceptibility to cancer, although study of this aspect of malignancy is a newly emerging field. (47) Such genetic factors include APC/MCC (45,46), RAS, DCC, p53 mutations and/or allelic losses, hyperexpression of c-MYC and RB genes. (10)
Mutation of the p53 tumor suppressor gene is the most frequently observed genetic lesion in human cancer; more than 50% of all human tumors examined to date have identifiable p53 gene point mutations or deletions. (4,5,6,7,14) While some p53 gene mutation is heritable, the majority of tumor suppressor gene mutation appears inducible, primarily by environmental factors. (8,9,11,12,13,15,16,17)
Although genetics undoubtedly play a role in susceptibility to cancer, it is estimated that less than 25% of all cancers are genetically related. (58)
2. 2.) Chronic viral infections. Chronic infections of Epstein-Barr(EBV) (18,19,20,21,32) ,Human Papilloma (HPV) (22,23,24,25), Hepatitis C (HCV) (26), Hepatitis B (HBV) (27), Cytomegalovirus (CMV) (28,29,30), human polyomaviruses JC(JCV) and BK (BKV) (31), and others predispose to cancer development.
3. 3.) Chronic inflammation.(32,33,34,35,36,37,38,39,40,41,42,43,44,47)
4. 4.) Toxins, both endogenous and exogenous, can initiate cancer by causing ROS which in turn damage DNA. A number of exogenous and endogenous chemicals are considered carcinogenic, although the rate and degree of internal detoxification, especially phase II liver enzymes, are an important part of the initiation process. Few substances are carcinogenic per se without contribution from faulty or under-functioning internal detoxification systems. (53,54,55,56,57,58,59)
5. 5.) Ionizing radiation. X-rays and other sources of ionizing radiation are known to cause DNA mutations consistent with cancer initiation. (60)
DNA damage alone is usually insufficient to initiate tumor development. If the DNA damage is repaired or the damaged cell is eliminated, the multi-step process of cancer development will be thwarted. If, however, mutagenic damage is not repaired and/or the damaged cell is not eliminated, and if the cellular environment is conducive to cell growth, then damaged cells can multiply. This stage is known as “progression” and it is a necessary step for the development of malignancy. Factors which promote malignant cell growth include:
1.) Nutritional deficiencies. Certain vitamins, minerals, trace minerals and phytonutrients act in a number of ways to thwart malignant cell promotion. The mechanisms of actions are many and varied but include ROS inactivation, upregulation of detoxification pathways, esp. phase II liver enzyme pathways, direct decrease or neutralization of carcinogenic compounds, and immune system enhancement. Deficiencies of any one of the nutrients involved in these protective processes can leave the organism vulnerable to the promotion phase of cancer development.(61,62,63,64,65,66,67,68,69,70,71)
2.) Extracellular milieu. Blood glucose, insulin, cortisol, and arachadonic-derived prostatglandins (especially PGE2) act as promoters. In hormone-responsive cancers, estrogens, testosterone, prolactin and sex hormone metabolites and mimickers can also promote cell growth. The metabolic state of the organism therefore plays a major role in the promotion of cancer. (72,73,74,75,76,77)
3.) Inflammation. In addition to being an initiator of cancer, inflammation also acts to promote cancer in several ways, primarily by altering the cell-to-cell communication and delaying local detoxification. (32,33,34,35,37,38,39,40)
Treatment strategies involve interfering with cancer progression at any phase of development, but initiation and promotion stages present the greatest opportunity for intervention.
To prevent the DNA damage which occurs during initiation, steps can be taken to mitigate sources of mutation, as follows:
I.) Genetic factors. While this aspect of initiation might seem the hardest to compensate for, it must be remembered that genetic mutation represents only weakness, not a forgone conclusion that cancer will develop. Minimizing other predispositions to initiation, such as nutrient deficiencies and carcinogenic exposure, can be sufficient to overcome heritable weaknesses. Further, dietary fasting, calorie restriction (CR) or a ketogenic diet (KD) have been shown to suppress the p53 oncogene, rendering this most common genetic factor less relevant. (78)
II.) Chronic viral infections. As with genetic factors, the presence of a chronic viral infection does not, by itself, mean an initiating certainly. Immune-enhancing strategies, anti-viral therapies and avoidance of other known initiators may be sufficient to prevent virally-caused mutagenesis.
III.) Chronic inflammation. Now known as a risk factor for heart disease, rheumatic disease and cancer, even subtle levels of inflammation, as measured by an hs-CRP blood test, can elevate risk of initiation. Fortunately, such inflammatory conditions respond well to nutritional, botanical and dietary modification. CR and KD have both been shown to reduce inflammation. Bromelain, curcumin and other anti-cancer drugs are, perhaps not coincidentally, also potent anti-inflammatory substances.
IV.) Toxins and radiation. Minimization of exposure and optimal dietary antioxidants can help offset the effects of environmental toxins, whether chemicals or ionizing radiation. Avoidance of exposure is also an obvious but often-overlooked preventive measure.
The Most Potent Anti-Cancer Strategy Known
“Attack by stratagem: hence, to fight and conquer in all your battles is not supreme excellence; supreme excellence consists in breaking the enemy’s resistance without fighting” —Sun Tzu, “The Art of War”
Nutritional and botanical factors can have profound positive effects in cancer treatment, either alone or as adjuncts to conventional treatment.
The single most potent anti-cancer strategy documented in the medical literature is to strike at the core of cancer’s metabolism: anaerobic glycolysis. Numerous animal and human studies have demonstrated that the glycolytic pathway of cancer cells can be confounded by the metabolic state of ketosis, often with profound apoptotic effects on cancer cells but without consequence to normal cells. In fact, the metabolic state of ketosis may curtail cancer growth by a number of different mechanisms:
I.) Greatly decreasing the glucose substrate required for cancer cell metabolism. Most tumors express abnormalities in the number and function of their mitochondria (80,81,88,89). Such abnormalities would prevent the bioenergetic utilization of ketone bodies, which require functional mitochondria for their oxidation.
II.) Decreasing insulin, a secondary growth factor for cancer cells.
III.) Decreasing inflammation (metabolic ketosis has anti-inflammatory effects). (85,86,87)
IV.) Decreasing ROS production. (82,83,84)
As one author pointed out, why would we believe that cells damaged by mutation are more resilient than normal cells? The answer is: they are not. Malignant cells are largely incapable of the metabolic flexibility displayed by normal cells, and therein lies their weakness and the potential for a gentle but highly effective point of attack.
Ketosis can be achieved by a high fat, moderate protein, low carbohydrate diet or by a calorie-restricted (CR) diet. Both methods of achieving ketosis have proven to decrease the production of ROS. Calorie restriction (CR) has a long history of experimentation in animals where it has also been seen to increase ROS antioxidant defense systems including superoxide dismutase, catalase, and glutathione peroxidase. (90)
In spite of improved availability of foods containing anti-carcinogenic phytonutrients and vitamins, many types of cancer have not declined as expected. This correlates to the overall calorie increase and overweight condition of our society, a condition which puts us in “constant feast” mode instead of the periodic fasting our ancestors previously experienced. (91) Many observers feel that our previous occasional fast, which would induce ketosis, was also beneficial for cancer control. It has also been hypothesized that some alternative cancer treatments, such as juice fasting or the use of Coley’s toxins, are effective primarily because they induce metabolic ketosis.
Additional Nutritional and Botanical Interventions
Although virtually any nutrient or herb can be considered in cancer treatment because of the multiple systems involved in same, only a relatively small handful of specific nutrients and botanicals have been well-studied and consistently proven to benefit the cancer patient. We will confine our discussion to those substances with a long history of use in human malignancy.
Nutritional Supplementation in the Treatment of Cancer
Supplements of proven utility in cancer treatment include:
I.) Vitamin C: long used for it’s dual function of immune up-regulation and direct toxicity to cancer cells, but doses sufficient to achieve the cytotoxic effect are unobtainable via the oral route. For this reason, IV vitamin C should be considered in cancer therapy. (92)
II.) Vitamin D3 (cholecalciferol): vitamin D deficiency is a known risk factor for cancer development.(93) D3 induces differentiation, inhibits angiogenesis (94, 95,96) and shows antitumor activity.(97,98,99) It may also up-regulate vitamin A receptors.(94) Vitamin D3 may serve to prevent metastatic bone disease in higher doses, perhaps because it is needed for normal calcification of bone matrix.
III.) Melatonin: a hormone produced by the pituitary gland which regulates sleep and circadian rhythms. Melatonin is a more potent antioxidant than glutathione or vitamin E (101). In vitro, it demonstrates anti-estrogen activity and immune stimulation. (100) Recent studies show that melatonin inhibits cell proliferation profoundly in vivo but only weakly in vitro. It is synergistic with IL-2 and increases the effectiveness of IL-2 treatment. (102)
IV.) CoQ10 (ubiquinone): this vitamin-like compound is involved in mitochondrial energy production. The heart is a high user of CoQ10 and many chemotherapeutic drugs deplete body stores of this nutrient. CoQ10 has been used successfully to reduce chemotherapy-induced cardio toxicity. In breast cancer patients, a dose of 90mg daily increases late stage survival dramatically. Three cases of complete remission have been documented at higher doses (300-400mg) per day. (103)
V.) Selenium: studies show that seleium interferes with the activity of p53 genes that promote the growth of cancer and induces apoptosis (104,105,106).
VI.) Tocotrienols: a member of the Vitamin E family, tocotrienols induce apoptosis and S-phase arrest (107,108) and inhibit proliferation. (109)
Botanical Considerations in Cancer Treatment
A HIGHLY SELECTIVE MATERIA MEDICA
Classified by action:
Natural Killer (NK) Cell Activation
Stimulants of IgG & IgM Production
Angelica sinensis-dong quai
Meliotus officinalis-sweet clover
Trifolium pratense- red clover
modified citrus pectin (MCP)
Cytotoxic (IV administration)
Catharanthus roseus- periwinkle
Taxus batacca- English yew- docetaxel
Taxus brevifolia- Pacific yew- paclitaxel
Viscum album-mistletoe- Iscador®]
Allium sativum (Liliaceae) – Garlic
As a food and a medicine, garlic comes closest to being a true panacea. Research has proved garlic’s immune-potentiating ability, including activation of NK and T-cells. (1,2,3,4.) Garlic is fibrinolytic, decreases platelet aggragation (5,6,7) and has been shown to have direct anti-tumor effects. 8,9,10. It is also a potent broad-spectrum antimicrobial, effective against alpha- and beta- Strep., E. coli., Klebsiella pneumonia, Mycobacterium, Salmonella, Staph. aureus, and Proteus spp. (17, 18, 19)
Aloe vera (Liliaceae) – Aloes
Acemannan, a water-soluable polysaccharide in Aloe vera, is a known immuno-stimulant (27,28) and anti-viral. (29) It’s mechanism of action is thought to be via stimulation of macrophage secretion of Tumor Necrosis Factor (TNF), interleukon, and interferon.
Ananas comosus (Bromeliaceae) – Pineapple (bromelain)
Bromelain is a sulfur-containing proteolytic enzyme from the stem of the pineapple plant. Other constituents include a non-proteolytic plasminogen activator, a peroxidase, and several protease inhibitors. (22,23)
Bromelain possesses significant anti-inflammatory activity by selective inhibition of pro-inflammatory prostaglandins. (16, 20) It also possesses fibrinolytic activity secondary to plasminogen activator (21) which may account for the antimetastatic properties seen in vivo. (24, 25, 26)
Astragalus membranaceus (Leguminosae) – Astragalus, Milk Vetch, Huang QI
Astragalus increases NK and T cell activity (11,12) in both normal and immunocompromised hosts.(13) It increases interferon production and is antibiotic against Shigella, Strep., Staph. and Diplococcus.(15)
Hydrastis Canadensis – (Ranunculaceae) – Goldenseal
Berberis aquafolia – (Berberidaceae) – Oregon Grape
Berberis vulgaris – (Berberidaceae) – Barberry
Berberine, an alkaloid derivative from various plants, has demonstrated significant antitumor effects with kill rates of 81% in vivo and 91% in vitro. This compares favorably to BCNU, a chemotherapeutic agent with a kill rate of 43% in vitro. (30)
Berberine sulfate also shows macrophage activation and cytostatic activity against tumor cells in vitro. (31) Berberine is well known for its broad spectrum antimicrobial activity (32,33,34) which is most effective in a neutral to alkaline medium. (35)
Angelica sinensis – (Umbelliferaceae) – Dong quai
Metolium officinalis – Sweet clover
Trifolium pretense – (Leguminosae) – Red clover
Coumarin (1,2-benzopyrone) is a component of several medicinal plants that have been used historically in the treatment of cancer. Recent research has shown an immunomodulatory effect through activation of macrophages and monocytes. (39)
Curcuma longa – (Zingiberaceae) – Turmeric
Curcumin, a major component in turmeric, is a potent antioxidant and hepatoprotectant. It has been shown to inhibit cancer in all stages of development (initiation, promotion, and progression), (36) and provide symptom relief when used topically on external cancers. (37)
Anti-inflammatory effects are believed due to its ability stabilize lysosomal membranes and uncouple oxidative phosphorylation. At higher doses, curcumin stimulates endogenous corticoid release. (38)
Echinacea purpura, E. angustifolia (Compositae) – Purple coneflower
Echinacea is one of the most widely studied medicinal herbs, and its immune-potentiating effects are not in question.
Arabinogalactin, a purified polysaccharide from E. purpura, has been shown to activate macrophage cytotoxicity to tumor cells, increase interferon production, stimulate T-lymphocyte production and activity, enhance NK cell activity and increase levels of circulating neutrophils. (40, 41, 42,43)
Echinacea stimulates non-specific defense mechanisms including alternate complement pathway. (44) It is anti-tumerogenic in animal models. (45)
Eleutherococcus senticosis – (Araliaceae) – Siberian ginseng
Eleutherococcus has been shown to both elevate numbers and activate helper / inducer lymphocytes and NK cells. (46)
It has been revered in Russia as an adaptogen, and studies confirm that it normalizes numerous physical functions regardless of the direction of imbalance. (47)
Larix occidentalis, L. dahurica – (Pinaceae) – Larch
Larch is a deciduous conifer that contains an arabinogalactan similar to that in other “immune enhancing” herbs including Echinacea spp., Baptisia tinctora, and Curcuma longa.
Larch arabinogalactans have been shown to reduce the number of liver metastasis in multiple studies (48,49,50,51), perhaps by acting as a “reverse lectin” and blocking tumor binding sites. (52) A similar effect has been noted for Modified Citrus Pectin (MCP). (See below)
Panax ginseng – (Araliaceae) – Chinese or Korean ginseng
Ginsenosides, an active constituent in P. ginseng, have been shown to increase both the number and the activity of lymphocytes in healthy subjects. (53)
Large doses in lab animals (human equivalent of 500 -125,000 mg) for five days increased IgG and IgM formation by 50 and 100% respectively, and enhanced NK cell activity and interferon production. (54)
Ginseng has long been considered an adaptogenic herb, and recent research verifies that it increases resistance to physical and chemical stress. (55,56)
Modified Citrus Pectin (MCP)
Pectin, a high molecular-weight polysaccharide present in the cell wall of all plants, can be pH degraded to produce a modified (smaller) polysaccharide with anti-metastatic capabilities. (57) MCP appears to bind with galectins on cancer cell surfaces, inhibiting aggregation and adherence to normal cells (58) and offering anti-metastatic protection in animal models. (59,60,61)
Much more is known about the management of cancer, including how to evoke durable remissions and even cure, than is generally used or discussed in conventional medicine. Perhaps this is because some of the most powerful and proven therapies do not require drugs or invasive intervention.
“Those who battle nature as their enemy will lose; those who use nature to battle their enemy will win.” —Mark Ziemann, R.N.
1.) Kandil O.M., et al.: Garlic and the immune system in humans: its effect on natural killer cells. Fed Proc 46:441, 1987.
2.) Morioka, N., Morton, D.L., and Irie, R.F.: A protein fraction from aged garlic extract enhances cytotoxicity and proliferation of human lymphocytes mediated by interleukin-2 and conavalin. Proc Ann Meet Am Assoc Cancer 34:A3297, 1993.
3.) Lau, B.H., Yamasaki, T., and Gridley, D.S.: Garlic compounds modulate macrophage and T-lymphocyte function. Mol Biother 3:103-107, 1991.
4.) Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49-53.
5.) Law JC, Whiteside TL, Gollin SM, Weissfeld J, El-Ashmawy L, Srivastava S, Landreneau RJ, Johnson JT, Ferrell RE.: Variation of p53 mutational spectra between carcinoma of the upper and lower respiratory tract. Clin Cancer Res. 1995 Jul;1(7):763-8.
6.) Harris CC: 1995 Deichmann Lecture–p53 tumor suppressor gene: at the crossroads of molecular carcinogenesis, molecular epidemiology and cancer risk assessment. Toxicol Lett. 1995 Dec;82-83:1-7.
7.) Kohler MF, Marks JR, Wiseman RW, Jacobs IJ, Davidoff AM, Clarke-Pearson DL, Soper JT, Bast RC Jr, Berchuck A.: Spectrum of mutation and frequency of allelic deletion of the p53 gene in ovarian cancer. J Natl Cancer Inst. 1993 Sep 15;85(18):1513-9.
8.) Puisieux A, Lim S, Groopman J, Ozturk M.: Selective targeting of p53 gene mutational hotspots in human cancers by etiologically defined carcinogens. Cancer Res. 1991 Nov 15;51(22):6185-9.
9.) Lasky T, Silbergeld E.:P53 mutations associated with breast, colorectal, liver, lung, and ovarian cancers. Environ Health Perspect. 1996 Dec;104(12):1324-31.
10.) Karakosta A, Golias Ch, Charalabopoulos A, Peschos D, Batistatou A, Charalabopoulos K.: Genetic models of human cancer as a multistep process. Paradigm models of colorectal cancer, breast cancer, and chronic myelogenous and acute lymphoblastic leukaemia. J Exp Clin Cancer Res. 2005 Dec;24(4):505-14.
11.) Sakaguchi S, Yokokawa Y, Hou J, Zhang XL, Li XP, Li SS, Li XX, Zhu DC, Kamijima M, Yamanoshita O, Nakajima T.: Environmental exposure and p53 mutations in esophageal cancer patients in areas of low and high incidence of esophageal cancer in China. Tohoku J Exp Med. 2005 Dec;207(4):313-24.
12.) Van Vleet TR, Watterson TL, Klein PJ, Coulombe RA Jr.: Aflatoxin B1 alters the expression of p53 in cytochrome P450-expressing human lung cells.Toxicol Sci. 2006 Feb;89(2):399-407. Epub 2005 Nov 9.
13.) Hong HH, Dunnick J, Herbert R, Devereux TR, Kim Y, Sills RC.: Genetic alterations in K-ras and p53 cancer genes in lung neoplasms from Swiss (CD-1) male mice exposed transplacentally to AZT. Environ Mol Mutagen. 2006 Jan 4; [Epub ahead of print]
14.) Le Roux E, Gormally E, Hainaut P.: Somatic mutations in human cancer: applications in molecular epidemiology. Rev Epidemiol Sante Publique. 2005 Jun;53(3):257-66.
15.) Ohgaki H, Kleihues P.: Epidemiology and etiology of gliomas. Acta Neuropathol (Berl). 2005 Jan;109(1):93-108. Epub 2005 Feb 1.
16.) Schroeder JC, Conway K, Li Y, Mistry K, Bell DA, Taylor JA.: p53 mutations in bladder cancer: evidence for exogenous versus endogenous risk factors. Cancer Res. 2003 Nov 1;63(21):7530-8.
17.) Gao WM, Romkes M, Day RD, Siegfried JM, Luketich JD, Mady HH, Melhem MF, Keohavong P. Association of the DNA repair gene XPD Asp312Asn polymorphism with p53 gene mutations in tobacco-related non-small cell lung cancer. Carcinogenesis. 2003 Oct;24(10):1671-6. Epub 2003 Jul 4.
18.) Foster AE, Rooney CM.: Improving T cell therapy for cancer. Expert Opin Biol Ther. 2006 Mar;6(3):215-29.
19.) Dutta N, Gupta A, Mazumder DN, Banerjee S. Down-regulation of locus-specific human lymphocyte antigen class I expression in Epstein-Barr virus-associated gastric cancer: implication for viral-induced immune evasion. Cancer. 2006 Apr 15;106(8):1685-93.
20.) Luo B, Wang Y, Wang XF, Gao Y, Huang BH, Zhao P.: Correlation of Epstein-Barr virus and its encoded proteins with Helicobacter pylori and expression of c-met and c-myc in gastric carcinoma. World J Gastroenterol. 2006 Mar 28;12(12):1842-8.
21.) Ng MH, Chan KH, Ng SP, Zong YS.: Epstein-Barr virus (EBV) latent membrane protein-1-specific cytotoxic T lymphocytes targeting EBV-carrying natural killer cell malignancies. Eur J Immunol. 2006 Mar;36(3):593-602.
22.)Doorbar J. Molecular biology of human papillomavirus infection and cervical cancer. Clin Sci (Lond). 2006 May;110(5):525-41.
23.)Castellsague X, Diaz M, de Sanjose S, Munoz N, Herrero R, Franceschi S, Peeling RW, Ashley R, Smith JS, Snijders PJ, Meijer CJ, Bosch FX; International Agency for Research on Cancer Multicenter Cervical Cancer Study Group: Worldwide human papillomavirus etiology of cervical adenocarcinoma and its cofactors: implications for screening and prevention. J Natl Cancer Inst. 2006 Mar 1;98(5):303-15.
24.)Karagas MR, Nelson HH, Sehr P, Waterboer T, Stukel TA, Andrew A, Green AC, Bavinck JN, Perry A, Spencer S, Rees JR, Mott LA, Pawlita M. Human papillomavirus infection and incidence of squamous cell and basal cell carcinomas of the skin. J Natl Cancer Inst. 2006 Mar 15;98(6):389-95.
25.)Zhao X, Rasmussen S, Perry J, Kiev J.The human papillomavirus as a possible cause of squamous cell carcinoma: a case study with a review of the medical literature. Am Surg. 2006 Jan;72(1):49-50.
26.) Yao F, Terrault N.: Hepatitis C and hepatocellular carcinoma. Curr Treat Options Oncol. 2001 Dec;2(6):473-83.
27.) Wong ET, Chew YP, Lee LA, Lee CG.: Therapeutic strategies for hepatitis B virus-associated hepatocellular carcinoma. Curr Drug Targets. 2002 Oct;3(5):369-78.
28.)Soderberg-Naucler C. Does cytomegalovirus play a causative role in the development of various inflammatory diseases and cancer? J Intern Med. 2006 Mar;259(3):219-46.
29.) Koch S, Solana R, Rosa OD, Pawelec G. Human cytomegalovirus infection and T cell immunosenescence: A mini review. Mech Ageing Dev. 2006 Feb 28; [Epub ahead of print]
30.)Pawelec G, Koch S, Gouttefangeas C, Wikby A. Immunorejuvenation in the elderly. Rejuvenation Res. 2006 Spring;9(1):111-6.
31.)Rollison DE, Engels EA, Halsey NA, Shah KV, Viscidi RP, Helzlsouer KJ.: Prediagnostic circulating antibodies to JC and BK human polyomaviruses and risk of non-Hodgkin lymphoma. Cancer Epidemiol Biomarkers Prev. 2006 Mar;15(3):543-50.
32.) Khan G.: Epstein-Barr virus, cytokines, and inflammation: A cocktail for the pathogenesis of Hodgkin’s lymphoma? Exp Hematol. 2006 Apr;34(4):399-406.
33.)Dalgleish AG, O’Byrne K. Inflammation and cancer: the role of the immune response and angiogenesis. Cancer Treat Res. 2006;130:1-38.
34.)Schottelius AJ, Dinter H.: Cytokines, NF-kappaB, microenvironment, intestinal inflammation and cancer. Cancer Treat Res. 2006;130:67-87.
35.)Otani T, Iwasaki M, Sasazuki S, Inoue M, Tsugane S.: Plasma C-reactive protein and risk of colorectal cancer in a nested case-control study: Japan public health center-based prospective study. Cancer Epidemiol Biomarkers Prev. 2006 Apr;15(4):690-5.
36.)Ernst P.: The role of inflammation in the pathogenesis of gastric cancer. Aliment Pharmacol Ther. 1999 Mar;13 Suppl 1:13-8
37.)Dobrovolskaia MA, Kozlov SV.: Inflammation and cancer: when NF-kappaB amalgamates the perilous partnership.Curr Cancer Drug Targets. 2005 Aug;5(5):325-44.
38.) Naldini A, Carraro F.: Role of inflammatory mediators in angiogenesis. Curr Drug Targets Inflamm Allergy. 2005 Feb;4(1):3-8.
39.)Ohshima H, Tazawa H, Sylla BS, Sawa T.: Prevention of human cancer by modulation of chronic inflammatory processes. Mutat Res. 2005 Dec 11;591(1-2):110-22. Epub 2005 Aug 3.
40.)Coussens LM, Werb Z.: Inflammation and cancer. Nature. 2002 Dec 19-26;420(6917):860-7.
41.)Chung LW, Baseman A, Assikis V, Zhau HE.: Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J Urol. 2005 Jan;173(1):10-20.
42.)Wang X, Wang E, Kavanagh JJ, Freedman RS.: Ovarian cancer, the coagulation pathway, and inflammation. J Transl Med. 2005 Jun 21;3:25.
43.)Dempke W, Rie C, Grothey A, Schmoll HJ.: Cyclooxygenase-2: a novel target for cancer chemotherapy? J Cancer Res Clin Oncol. 2001 Jul;127(7):411-7.
44.)Jackson L, Evers BM.: Chronic inflammation and pathogenesis of GI and pancreatic cancers. Cancer Treat Res. 2006;130:39-65.
45.)Sanz-Ortega J, Sanz-Esponera J, Caldes T, Gomez de la Concha E, Sobel ME, Merino MJ. LOH at the APC/MCC gene (5Q21) in gastric cancer and preneoplastic lesions. Prognostic implications. Pathol Res Pract. 1996 Dec;192(12):1206-10.
46.)Fang DC, Jass JR, Wang DX, Zhou XD, Luo YH, Young J. Infrequent loss of heterozygosity of APC/MCC and DCC genes in gastric cancer showing DNA microsatellite instability. J Clin Pathol. 1999 Jul;52(7):504-8.
47.) de Visser K, Eichten A., Coussens L.,: Paradoxical roles of the immune system during cancer development. Nature Reviews Cancer 6, 24-37 (January 2006).
48.) Stephen D. Hursting, Thomas J. Slaga, Susan M. Fischer, John DiGiovanni, James M. Phang: Mechanism-Based Cancer Prevention Approaches: Targets, Examples, and the Use of Transgenic Mice. Journal of the National Cancer Institute, Vol. 91, No. 3, 215-225, February 3, 1999.
49.) Slaga TJ. Mechanisms involved in two-stage carcinogenesis in mouse skin. In: Slaga TJ, editor. Mechanisms of tumor promotion. Boca Raton (FL): CRC Press; 1984. p. 1-93.
50.) Sugimura T.: Multistep carcinogenesis: a 1992 perspective. Science. 1992 Oct 23;258(5082):603-7.
51.) Guengerich FP.: Metabolic activation of carcinogens. Pharmacol Ther. 1992;54(1):17-61.
52.) IB Weinstein: The origins of human cancer: molecular mechanisms of carcinogenesis and their implications for cancer prevention and treatment–twenty-seventh G.H.A. Clowes memorial award lecture. Cancer Research, Vol 48, Issue 15 4135-4143.
53.)Rydlova H, Miksanova M, Ryslava H, Stiborova M.: Carcinogenic pollutants o-nitroanisole and o-anisidine are substrates and inducers of cytochromes P450.Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2005 Dec;149(2):441-7.
54.)Luersen L, Wellner T, Koch HM, Angerer J, Drexler H, Korinth G.: Penetration of beta-naphthylamine and o-toluidine through human skin in vitro. Arch Toxicol. 2006 Apr 5; [Epub ahead of print].
55.)Paustenbach DJ, Fehling K, Scott P, Harris M, Kerger BD.:Identifying soil cleanup criteria for dioxins in urban residential soils: how have 20 years of research and risk assessment experience affected the analysis? J Toxicol Environ Health B Crit Rev. 2006 Mar-Apr;9(2):87-145.
56.) Zahid M, Kohli E, Saeed M, Rogan E, Cavalieri E.: The greater reactivity of estradiol-3,4-quinone vs estradiol-2,3-quinone with DNA in the formation of depurinating adducts: implications for tumor-initiating activity. Chem Res Toxicol. 2006 Jan;19(1):164-72.
57.) Perchellet JP, Perchellet EM, Gali HU, Gao XM. Oxidant stress and multistage carcinogenesis. In: Mukhtar H, editor. Skin cancer: mechanisms and human relevance. Boca Raton (FL): CRC Press; 1995. p. 145-80.
58.) Foundations of Wellness, U.C. Berkley Wellness Newsletter, April 2006.
59.)Bounias M.: Etiological factors and mechanism involved in relationships between pesticide exposure and cancer. J Environ Biol. 2003 Jan;24(1):1-8.
60.) JE Moulder: Power-frequency fields and cancer. Crit Rev Biomed Eng 26:1-116, 1998.
61.)Grubben MJ, van den Braak CC, Nagengast FM, Peters WH.: Low colonic glutathione detoxification capacity in patients at risk for colon cancer. Eur J Clin Invest. 2006 Mar;36(3):188-92.
62.)Davenport DM, Wargovich MJ.: Modulation of cytochrome P450 enzymes by organosulfur compounds from garlic. Food Chem Toxicol. 2005 Dec;43(12):1753-62.
63.)Yang P, Ebbert JO, Sun Z, Weinshilboum RM.: Role of the glutathione metabolic pathway in lung cancer treatment and prognosis: a review. J Clin Oncol. 2006 Apr 10;24(11):1761-9.
64.)Grandics P.: Cancer: a single disease with a multitude of manifestions? J Carcinog. 2003 Nov 18;2(1):9.
65.)Ahluwalia N.: Aging, nutrition and immune function. J Nutr Health Aging. 2004;8(1):2-6.
66.)Campbell SE, Stone WL, Lee S, Whaley S, Yang H, Qui M, Goforth P, Sherman D, McHaffie D, Krishnan K.: Comparative effects of RRR-alpha- and RRR-gamma-tocopherol on proliferation and apoptosis in human colon cancer cell lines. BMC Cancer. 2006 Jan 17;6:13.
67.)Chen C, Kong AN.: Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects. Trends Pharmacol Sci. 2005 Jun;26(6):318-26.
68.) Mehta R, Laver GW, Stapley R, McMullen E.: Liver DNA adducts in methyl-deficient rats administered a single dose of aflatoxin B1. Carcinogenesis. 1992 Jul;13(7):1241-7.
69.) Ghoshal AK, Farber E.: Choline deficiency, lipotrope deficiency and the development of liver disease including liver cancer: a new perspective. Lab Invest. 1993 Mar;68(3):255-60.
70.)Tuohimaa P, Lyakhovich A, Aksenov N, Pennanen P, Syvala H, Lou YR, Ahonen M, Hasan T, Pasanen P, Blauer M, Manninen T, Miettinen S, Vilja P, Ylikomi T.: Vitamin D and prostate cancer. J Steroid Biochem Mol Biol. 2001 Jan-Mar;76(1-5):125-34.
71.)Ryan BM, Weir DG.: Relevance of folate metabolism in the pathogenesis of colorectal cancer. J Lab Clin Med. 2001 Sep;138(3):164-76.
72.)Rapp K, Schroeder J, Klenk J, Ulmer H, Concin H, Diem G, Oberaigner W, Weiland SK.Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria. Diabetologia. 2006 Mar 24; [Epub ahead of print]
73.)Beck SA, Tisdale MJ. Effect of insulin on weight loss and tumour growth in acachexia model.Br J Cancer. 1989 May;59(5):677-81
74.) Fearon KC.: Nutritional pharmacology in the treatment of neoplastic disease. Baillieres Clin Gastroenterol. 1988 Oct;2(4):941-9.
75.) Bauer M, Hamm AC, Bonaus M, Jacob A, Jaekel J, Schorle H, Pankratz MJ, Katzenberger JD.: Starvation response in mouse liver shows strong correlation with life-span-prolonging processes. Physiol Genomics. 2004 Apr 13;17(2):230-44.
76.) Morita T, Tabata S, Mineshita M, Mizoue T, Moore MA, Kono S.: The metabolic syndrome is associated with increased risk of colorectal adenoma development: the Self-Defense Forces health study. Asian Pac J Cancer Prev. 2005 Oct-Dec;6(4):485-9.
77.) Tabuchi M, Kitayama J, Nagawa H.: Hypertriglyceridemia is positively correlated with the development of colorectal tubular adenoma in Japanese men. World J Gastroenterol. 2006 Feb 28;12(8):1261-4.
78.) Berrigan D, Perkins SN, Haines DC, Hursting SD.: Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis. 2002 May;23(5):817-22.
79.)Stopper H, Schinzel R, Sebekova K, Heidland A.: Genotoxicity of advanced glycation end products in mammalian cells. Cancer Lett. 2003 Feb 20;190(2):151-6.
80.) Meixensberger J, Herting B, Roggendorf W, Reichmann H: Metabolic patterns in malignant gliomas.J Neurooncol 1995, 24:153-161
81.) Pedersen PL: Tumor mitochondria and the bioenergetics of cancer cells. Prog Exp Tumor Res 1978, 22:190-274.
82.) Veech RL: The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot Essent Fatty Acids 2004, 70:309-319.
83.) Veech RL: Metabolic control analysis of ketone and insulin action: Implications for phenotyping of disease and design of therapy.Lecture: The Dynamic and Energetic Basis of Health and Aging Monday, Nov 11 – Wednesday, Nov 13, 2002, The Cloister’s, NIH, Bethesda MD
84.) Masuda R, Monahan JW, Kashiwaya Y: D-beta-hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures. J Neurosci Res 2005, 80:501-509.
85.) Stewart JW, Koehler K, Jackson W, Hawley J, Wang W, Au A, Myers R, Birt DF: Prevention of mouse skin tumor promotion by dietary energy restriction requires an intact adrenal gland and glucocorticoid supplementation restores inhibition.Carcinogenesis 2005, 26:1077-1084
86.) Zhu Z, Jiang W, Thompson HJ: Mechanisms by which energy restriction inhibits rat mammary carcinogenesis: in vivo effects of corticosterone on cell cycle machinery in mammary carcinomas. Carcinogenesis 2003, 24:1225-1231.
87.) Patel NV, Finch CE: The glucocorticoid paradox of caloric restriction in slowing brain aging.Neurobiol Aging 2002, 23:707-717.
88.) Seyfried TN, Sanderson TM, El-Abbadi MM, McGowan R, Mukherjee P.: Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.Br J Cancer. 2003 Oct 6;89(7):1375-82.
89.) Fearon KC.: Nutritional pharmacology in the treatment of neoplastic disease.Baillieres Clin Gastroenterol. 1988 Oct;2(4):941-9.
90.) Weindruch R, Walford RL, editors. The retardation of aging and disease by dietary restriction. Springfield (IL): C. Thomas; 1988. p. 1-291
91.) Wargovich MJ, Cunningham JE.:Diet, individual responsiveness and cancer prevention. J Nutr. 2003 Jul;133(7 Suppl):2400S-2403S.
92.)Padayatty SJ, Riordan HD, Hewitt SM, Katz A, Hoffer LJ, Levine M.: Intravenously administered vitamin C as cancer therapy: three cases.CMAJ. 2006 Mar 28;174(7):937-42.
93.)Holick MF.: Vitamin D: Its role in cancer prevention and treatment. Prog Biophys Mol Biol. 2006 Mar 10; [Epub ahead of print]
94.) Majewski S, Skopinska M, Marczak M, Szmurlo A, Bollag W, Jablonska S.: Vitamin D3 is a potent inhibitor of tumor cell-induced angiogenesis. J Investig Dermatol Symp Proc. 1996 Apr;1(1):97-101.
95.) Majewski S, Szmurlo A, Marczak M, Jablonska S, Bollag W.: Synergistic effect of retinoids and interferon alpha on tumor-induced angiogenesis: anti-angiogenic effect on HPV-harboring tumor-cell lines.Int J Cancer. 1994 Apr 1;57(1):81-5.
96.) Majewski S, Szmurlo A, Marczak M, Jablonska S, Bollag W.: Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination.Cancer Lett. 1993 Nov 30;75(1):35-9.
97.) Wietrzyk J, Pelczynska M, Madej J, Dzimira S, Kusnierczyk H, Kutner A, Szelejewski W, Opolski A.: Toxicity and antineoplastic effect of (24R)-1,24-dihydroxyvitamin D3 (PRI-2191).Steroids. 2004 Sep;69(10):629-35.
98.) Vegesna V, O’Kelly J, Said J, Uskokovic M, Binderup L, Koeffle HP.: Ability of potent vitamin D3 analogs to inhibit growth of prostate cancer cells in vivo. Anticancer Res. 2003 Jan-Feb;23(1A):283-9.
99.) Schwartz GG, Eads D, Rao A, Cramer SD, Willingham MC, Chen TC, Jamieson DP, Wang L, Burnstein KL, Holick MF, Koumenis C.:Pancreatic cancer cells express 25-hydroxyvitamin D-1 alpha-hydroxylase and their proliferation is inhibited by the prohormone 25-hydroxyvitamin D3.Carcinogenesis. 2004 Jun;25(6):1015-26. Epub 2004 Jan 23.
100.) Reiter RJ, Melchiorri D, Sewerynek E, Poeggeler B, Barlow-Walden L, Chuang J, Ortiz GG, Acuna-Castroviejo D.: A review of the evidence supporting melatonin’s role as an antioxidant.J Pineal Res. 1995 Jan;18(1):1-11.
101.) Hill SM, Spriggs LL, Simon MA, Muraoka H, Blask DE.:The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system. Cancer Lett. 1992 Jul 10;64(3):249-56.
102.) Lissoni P, Barni S, Cazzaniga M, Ardizzoia A, Rovelli F, Brivio F, Tancini G.: Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone.Oncology. 1994 Jul-Aug;51(4):344-7.
103.) Boik, John: Cnacer and Natural Medicine, Oregon Medical Press, 1995,p.71.
104.) Drake EN.: Cancer chemoprevention: Selenium as a prooxidant, not an antioxidant. Med Hypotheses. 2006 Mar 28; [Epub ahead of print]
105.) Zhao R, Xiang N, Domann FE, Zhong W.: Expression of p53 enhances selenite-induced superoxide production and apoptosis in human prostate cancer cells.Cancer Res. 2006 Feb 15;66(4):2296-304.
106.) Sieber F, Daziano JP, Gunther WH, Krieg M, Miyagi K, Sampson RW, Ostrowski MD, Anderson GS, Tsujino I, Bula RJ.: ELEMENTAL SELENIUM GENERATED BY THE PHOTOBLEACHING OF SELENOMEROCYANINE PHOTOSENSITIZERS FORMS CONJUGATES WITH SERUM MACROMOLECULES THAT ARE TOXIC TO TUMOR CELLS.Phosphorus Sulfur Silicon Relat Elem. 2005;180(3-4):647-657.
107.) Wada S, Satomi Y, Murakoshi M, Noguchi N, Yoshikawa T, Nishino H.: Tumor suppressive effects of tocotrienol in vivo and in vitro.Cancer Lett. 2005 Nov 18;229(2):181-91. Epub 2005 Aug 10.
108.) Sylvester PW, Shah SJ, Samant GV.: Intracellular signaling mechanisms mediating the antiproliferative and poptotic effects of gamma-tocotrienol in neoplastic mammary epithelial cells.J Plant Physiol. 2005 Jul;162(7):803-10
109.) Shah SJ, Sylvester PW.: Gamma-tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity. Exp Biol Med (Maywood). 2005 Apr;230(4):235-41.
Materia Medica References:
1.) Kandil O.M., et al.: Garlic and the immune system in humans: its effect on natural killer cells. Fed Proc 46:441, 1987.
2.) Morioka, N., Morton, D.L., and Irie, R.F.: A protein fraction from aged garlic extract enhances cytotoxicity and proliferation of human lymphocytes mediated by interleukin-2 and conavalin. Proc Ann Meet Am Assoc Cancer 34:A3297, 1993.
3.) Lau, B.H., Yamasaki, T., and Gridley, D.S.: Garlic compounds modulate macrophage and T-lymphocyte function. Mol Biother 3:103-107, 1991. 4.) Kandil, O.M. et. al.: Garlic and the immune system in humans: Its effect on natural killer cells. Fed Proc 46:441, 1987.
5.) Legnani C., Frascaro M., Guazzaloca G., et al.: Effects of a dried garlic preparation on fibrinolysis and platelet aggragation in healthy subjects. Arzneim Forsch Drug Res 43:119-122, 1993.
6.) Kiesewetter H., et al.: effects of garlic coated tablets in peripheral arterial occlusive disease. Clin Investig 71:383-86, 1993.
7.) Orekhov, A.N., et al.: Direct anti-atherosclerotic related effects of garlic. Ann Med 27:63-65, 1995.
8.) Belman S.: Onion and garlic oils prohibit tumor promotion. Carcinogenesis 4(8):1063-5, 1983.
9.) Dausch JG., Nixon DW.: Garlic: a review of its relationship to malignant disease. Prev Med 19:346-61, 1990.
10.) Kroning, F.: Garlic as an inhibitor for spontaneous tumors in predisposed mice. Acta Unio Inter Contra Cancrum 20(3):855, 1964.
11.) Yang, Y.Z., et al.: Effect of Astragalus membranaceus on natural killer cell activity and induction with coxsacke B viral myocarditis. Chin Med J 103:304-7, 1990.
12.) Zhao,K.S., Manici, C., and Doria, G.: Enhancement of the immune response in mice by Astragalus membranaceus. Immunopharmacol 20:225-33, 1990.
13.) Chu, D.T., et al.: Immunotherapy with Chinese medicinal herbs, I: Immune restoration of local xenogenic graft-versus-host reaction in cancer patients by fractionated Astragalus membranaceus in vitro. J Clin Lab Immunol 25:119-123, 1988.
15.) Yunde, H., Guoling, M., Shuhua, W., et al.: Effect of radix Astragalus seuhedysari on the interferon system. Chin Med J 94:35-40, 1981.
16.) Taussig,S.: The mechanism of the physiological action of bromelain. Med Hypothesis 6:99-104, 1980.
17.) Sharma, V.D., et al.: Antibacterial properties of Allium sativum Linn.: In vivo and in vitro studies. Ind J Exp Biol 15:466-468, 1977.
18.) Cavallito, C.J., and Bailey, J.H.: Allicin, the antibacterial principal in Allium sativum, I: Isolation, physical properties, and antibacterial action. J Am Chem Soc 66:1950-51,1944.
19.) Elnima, E.I. et al.: The antimicrobial activity of garlic and onion extracts. Pharmazie 38:747-48, 1983.
20.) Taussig, S., Batkin, S.: Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharm 22:191-203, 1988.
21.) Felton, G.E.: Fibrinolytic and antithrombotic action of bromelain may eliminate thrombosis in heart patients. Med Hypothesis, 6: 1123-33, 1980.
22.) Felton, G.E.: Does kinin released by pineapple stem bromelain stimulate production of prostaglandin E1-like compounds? Hawaii Med J 36:39-47, 1977.
23.) Taussig SJ.: The mechanism of the physiological action of bromelain. Med Hypothesis 6:99-104, 1980.
24.) Batkin, S., et al.: Modulation of pulmonary metastasis (Lewis lung carcinoma) by bromelain, an extract of the pineapple stam (Ananas comosus). Letter. Cancer Invest 6(2):241-242, 1988.
25.) Goldstein N., et al.: Bromelain as a skin cancer preventive in hairless mice. Hawaii Med J, 34:91-4, 1975.
26.) Gerard G., Therapeutique anti-cancreuse et bromelaines. Agressologie 3:261-274, 1972. (In French).
27.) Sheets, MA., Unger, BA., Giggleman GF Jr., Tizard, IR.: Studies of the effect of acemannan on retrovirus infections: Clinical stabilization of feline leukemia virus-infected cats. Mol Biother 3(1):41-45, 1991.
28.) Peng, SY., Norman J., Curtin G., et al.: Decreased mortality of Norman murine sarcoma in mice treated with the immunomodulator, acemannan. Mol Biother 3(2): 79-87, 1991.
29.) Kahlon, J.B., et al.: In vitro evaluation of the synergistic antiviral effects of acemannan in combination with azidothymidine and acyclovir. Mol Biother 3:214-23, 1991.
30.) Rong-xun Z., et al.: Laboratory studies of berberine used alone and in combination with 1,3bis (2-chloroethyl)-1-nitrosurea to treat malignant brain tumors. Chinese Med J 103(8):658-65, 1990.
31.) Kumazawa Y., et al.: Activation of peritoneal macrophages by berberine-type alkaloids in terms of induction of cytostatic activity. Int J Immunopharmacol 6(6):587-92, 1984.
32.) Hahn, F.E., Ciak, J.: Berberine. Antibiotics 3:577-88, 1976.
33.) Ghosh, A.K.: effect of berberine chloride on leishmania donovani. Ind J Med Res 78:407-16, 1983.
34.) Subbaiah, T.V., Amin, A.H.: Effect of berberine sulfate on E. histolytica. Nature 215:527-28, 1967.
35.) Amin, A.H., Subbaiah, T.V., and Abbasi, K.M.: Berberine sulfate: Antimicrobial activity, bioassay, and mode of action. Can J Microbiol 15:1067-76. 1969.
36.) Nagabhushan, M., Bhide, SV.: Curcumin as an inhibitor of cancer. J Am Col Nutr 11(2):192-8, 1992.
37.) Kuttan, R., Sudheeran PC., Josep CD.: Turmeric and curcumin as topical agents in cancer therapy. Tumori (Italy) 73:29-31, 1987.
38.) Srivastava R, Srimal, RC.: Modification of certain inflammation-induced biochemical changes by curcumin. Ind J Med Res 81:215-223, 1985.
40.) Luettig, B., et al.: Macrophage activation by the polysaccharide arabinogalactan isolated from plant cell cultures of Echinacea purpurea. J Natl Cancer Inst 81(9):669-75, 1989.
41.) Wagner, V.., Proksch, A., Zeitschrift Feur Agnewande Phytotherapie (German) 2(5):166-168, 171, 1981.
42.) Wagner, V., Proksch,A., Riess-Maurer,I., et al.: Immunostimulatin polysaccharides (heteroglycane) of higher plants: Preliminary communications. Arzneim Forsch 34:659-60, 1984.
43.) Mose, J.: Effect of echinacin on phagocytosis and natural killer cells. Med Welt 34:1463-67,1983.
44.) Vomel,V.: Influence of a non-specific immune stimulant on phagocytosis of erythrocytes and ink by the reticuloendothelial system of isolated perfused rat livers of different ages. Arzneim Forsch 34:691-95, 1984.
45.) Bauer, R., Jurcic, K., Puhlmann,J., Wagner, H.: Immunological in vivo and in vitro examinations of Echinacea extracts. Arzneim Forsch 38:276-281, 1988.
46.) Bohn,B., Nebe, C.T., Birr, C.: Flow-cytometric studies with Eleutherococcus senticosus extracts as an immunomodulatory agent. Arzneim-Forsch 37:1193-96, 1987.
47.) Pizzorno, J.E., Murray, M.T.: Eleutherococcus senticosus: A Textbook of Natural Medicine, Bastyr University Publications, Seattle, WA, 1995.
48.) Hagmar, B., Ryd, W., Skomedal, H.: Arabinogalactan blockade of experimental metastasis to liver by murine hepatoma. Invasion Metastasis 11(6):348-55, 1991.
49.) Uhlenbruck G., Beuth J., Roszkowski W., et al.: Prevention of experimental liver metastasis by arabinogalactan. Naturwissenschaften 73(10)626-7, Oct. 1986.
50.) Beuth J., Ko HL., Oette K., et al.: Inhibition of liver metastasis in mice by blocking hepatocyte lectins with arabinogalactan infusions and D-galactose. J cancer Res Clin Oncol 113(1): 51-5,1987.
51.) Beuth J., Ko HL., et al.: Inhibition of liver tumor cell colonization in two animal tumor models by lectin blocking with D-galactose or arabinogalacan. Clin Exp Metastasis 6(2):115-20, Mar-Apr 1988.
52.) D’Adamo, P.: Larch arabinogalactan. J Nat Med 6(1):33-36, 1996.
53.) Scaglione, F., et al.: Immunomodulatory effects of two extracts of Panax ginseng. Drugs Exp Clin Res 16:537-42, 1990.
54.) Jie, Y.H., Cammisuli,S., Baggiolini, M.: Immunomodulatory effects of Panax ginseng C.A. Meyer in the mouse. Agents Actions 15: 386-91, 1984.
55.) Bahrke M.S., Morgan W.P.: Evaluation of the ergogenic properties of ginseng. Sports Med 18: 229-48, 1994.
56.) Brekhman I., Dardymov I.V.: Pharmacological investigation of glycosides from ginseng and eleutherococcus. Lloydia 32:46-51, 1969.
57.) Kidd, P.M.: A new approach to metastatic cancer prevention: modified citrus pectin (MCP), a unique pectin that blocks cell surface lectins. Alt Med Rev 1(1): 4-10, 1996.
58.) Sharon N., Lis H.: Lectins as cell recognition molecules. Science 246:227-34, 1989.
59.) Platt D., Raz A.: Modulation of the lung colonization of B16-F1 melanoma cells by citrus pectin. J Natl Cancer Inst 84:438-442, 1992.
60.) Pienta KJ., et al.: Inhibition of spontaneous metastasis in a rat prostate cancer model by oral administration of modified citrus pectin. J Natl Cancer Inst 87:348-53, 1995.
61.) Raz, A., Lotan R.: Endogenous galactoside-binding lectins: a new class of functional cell surface molecules related to metastasis. Cancer Metastasis Rev 6:433-52, 1987.