Abstract:
The natural killer (NK) cell activity blood test is useful in predicting the prognosis of a cancer patient. The purpose of this in-office, nonrandomized open-label trial was to determine whether four different dietary supplements commonly sold in health food stores and over the Internet, consistently and statistically affected NK cell activity in cancer patients. Thirty-four patients were assigned to one of four groups: Group A was given 1-3g/day of modified arabinoxylane with meals. Group B was given 6000mg/day of coriolus mushroom. Group C was given 4g/day of antigen-infused dialyzable bovine colostrum/whey extract and group D was given 3-6g/day of active hexose correlated compound (AHCC). NK cell activities were assessed before treatment and after an average of 16 weeks of therapy. AHCC was the only supplement that consistently and statistically increased NK cell activity. The average increase was 249%. Modified arabinoxylane statistically increased NK cell activity, but did not consistently help every patient. No side effects were encountered during the study period in any of the four groups.
Introduction
Despite recent advances in oncology, a substantial amount of people with cancer are dying in less than five years (See table 1). (1)
To help improve these survival rates it may be important to identify and correct various adverse prognostic indicators. One negative prognostic indicator is low natural killer (NK) cell activity. Natural killer cells comprise between 5-20% of the peripheral blood lymphocytes and are capable of recognizing and killing tumor cells that completely lack expression of MHC Class I and II antigens. (2) The ability of a cancer patient's NK cells to lyse cancer cells can be determined by a 4-hr [.sup.51]chromium-release assay. Studies have shown that cancer patients with a low activity of NK cells have shorter remissions, greater tumor burdens and an increased risk for nodal metastasis. Response rates to chemotherapy may be lower and recurrence rates after surgery may be higher in patients with low baseline NK cell activities. It is also not uncommon for the activity of NK cells to decrease just prior to a recurrence in a patient's cancer. (3-22)
It may be possible to improve a cancer patient's prognosis by maintaining a high NK cell activity level. Several studies have demonstrated improved survival rates after activated killer cells are transferred into cancer patients. Transplanting activated killer cells into people, however, may create unwanted side effects, (23,24) therefore, activating the natural killer cells via an oral route may be a better choice. Various natural substances such as coriolus mushroom, active hexose correlated compound (AHCC), modified arabinoxylane and antigen-infused dialyzable bovine colostrum/whey extract have been described as oral NK cell activators in articles and advertisements. The purpose of this in-office study was to determine if these products consistently and significantly affected NK cell activity in cancer patients as advertised.
Material and Methods
Patients
This study was a nonrandomized, open-label trial in patients with a cancer diagnosis and was carried out in the author's office beginning in 2002. Thirty-six patients completed the study, but two were dropped from the statistical analysis because they were both taking high doses of fish oil and borage oil. Studies have shown that high doses of these oils severely decrease NK cell activity by decreasing levels of leukotriene-B4, a strong NK cell activator. (25,26) The 34 patients analyzed had various types of cancer in different stages. They consisted of 26 females and 8 males ranging from two to 72 years of age. None of the patients were taking a NK cell activator prior to the commencement of the study. The patients were divided into 4 groups. Group A, consisting of 15 patients, was treated with modified arabinoxylane. Group B, consisting of 8 patients, was treated with coriolus mushroom. Group C, consisting of 3 patients, was treated with antigen-infused dialyzable bovine colostrum/whey extract and group D. consisting of 8 patients, was treated with AHCC. Each group was allowed to take other nutritional supplements during the test period. Many of the same supplements were taken amongst the four groups. None of the allowed nutritional supplements, however, have been demonstrated to increase NK cell activity.
Modified arabinoxylane Group (Group A: n=15)
Modified arabinoxylane is a polysaccharide from rice bran that contains beta 1,4-xylopyranose hemicellulose that has been enzymatically treated with an extract from hyphomycetes mycelia (shiitake mushroom). Modified arabinoxylane was given in either a caplet or capsule form in a dose of 1000mg three times daily with meals and two hours away from other supplements. If the patient was taking the product longer than two months, the dose was reduced to 1000mg once daily with food. Modified arabinoxylane was chosen for this study because one human trial showed this substance increased NK cell activity by five-fold in 24 healthy individuals after eight weeks of treatment. (27)
Coriolus Group (Group B: n=8)
Coriolus versicolor is a mushroom commonly used in traditional Chinese and Japanese medicine. Hot water extracts of this mushroom contain 1-4, 1-3 polysaccharides (beta glucans) which are described to have immunomodulating properties. (28-30)
The coriolus product used in this study contained both the mycelium and young fruit body of the coriolus versicolor mushroom. Each 500mg tablet of Coriolus was standardized for about 63mg of protein-bound polysaccharides. Each patient in this group was given a doso of 2000mg three times a day with meals to provide a total of 756mg/day of protein-bound polysaccharides.
Antigen-Infused Dialyzable Bovine Colostrum/Whey Extract Group (Group C: n=3)
Antigen-Infused Dialyzable Bovine Colostrum/Whey Extract is an extract of the low molecular weight molecules naturally found in bovine whey. Cows are infused with antigens shortly before parturition. After delivery, the colostrum is collected and filtered to completely remove the whey proteins, antibodies and other higher-molecular weight molecules. (31,32) The author chose this product after reading material describing this substance as a powerful NK cell activator. Each capsule used in this study contained 50mg of Antigen-Infused Dialyzable Bovine Colostrum/Whey Extract 150mg of arabinogalactan, 25mg of astragalus root and 25mg of maitake mushroom 4:1. Patients were instructed to take four capsules twice a day with food for a total of 400mg/day of Antigen-Infused Dialyzable Bovine Colostrum/Whey Extract.
AHCC Group (Group D: n=8)
Active hexose correlated compound or AHCC contains a mixture of low molecular weight oligosaccharides enzymatically extracted from a myceloid of several species of Basidiomycete mushrooms including shiitake, which are cultured in a liquid medium with rice bran. Three grams per day of AHCC was demonstrated in one human trial to increase NK cell activity an average of 2.5-fold in nine out of eleven cancer patients after two weeks of therapy. (33) Each patient in this group took 2000mg of AHCC three times a day with meals. If they were taking the product longer than two months, the dose was reduced to 1000mg three times a day with food.
NK cell cytotoxicity assay
All patients had blood drawn before they began taking their assigned product to determine their baseline NK cell activity. All NK cell cytotoxicity assays were performed by Immunosciences Lab. Inc (Beverly Hills, California) using a standard 4-hr [.sup.51]Cr-release assay as described by Vojdani et al. 2004. (34) The results of NK cell assays were expressed in terms of lytic units (LU) calculated as described by Whiteside et al (1990). (35) Normal ranges for this test are between 20-50 lytic units.
Compliance
Compliance was determined by how often patients purchased their supplements from the author's office using Quickbooks software and through patients' verbal confirmation. Every patient chosen for this study was fully compliant.
Statistics
The data was analyzed statistically by the paired-t test.
Results
As shown in Table 2, the average increase in NK cell activity in the modified arabinoxylane group as a whole was significant, but the results varied considerably between patients. Modified arabinoxylane tripled NK cell activity in only four out of the fifteen patients in this group. The NK cell activity in 27% of patients actually decreased despite taking the recommended dose for an average of 15 weeks (4-50 weeks). Many of these patients were not on chemotherapy.
Continued from page 1.As shown in Tables 3 & 4, no significant changes were observed in NK cell activity in the patients given coriolus mushroom or antigen-infused dialyzable bovine colostrum/whey extract. Fifty percent of patients in fact, had a decrease in NK cell activity after an average of nine weeks on coriolus. Two out of the three patients given antigen-infused dialyzable bovine colostrum/whey extract had a decrease in NK cell activity after taking 400mg/day for an average of 7.5 weeks (4-7 weeks).
AHCC was the only product that consistently and significantly increased NK cell activity in all patients including those on chemotherapy. (See Table 5.) The average increase was 249% (166-469%) after a mean of 8 weeks (3-14 weeks).
No side effects were reported in any patient on any of the four treatments during the experimental period.
Discussion
Monitoring NK cell activity during follow-up office visits and correcting abnormalities with an oral NK cell activator may increase survival rates in cancer patients in remission and may prevent cancer occurrences in high risk groups. (3-22, 28-30) Strayer et al. reported that NK cell activities are consistently lower in people with a family history of cancer compared to individuals with a low familial incidence of cancer. Strayer et al. also reported that NK activity is inversely related to the number of family members with cancer. (36) Nakajima et al. reported that patients with cirrhosis of the liver have a higher risk of hepatocellular carcinoma if their NK cell activities are low. (37) In an eleven year study of 2196 women, Imai et al. found that women with a high NK cytotoxic activity (>51%) had approximately half the risk of cancer compared with those with a low NK cytotoxic activity ([less than or equal to]34%). (38)
In this study, only AHCC significantly and consistently increased NK cell activity levels in cancer patients. Modified arabinogalactan statistically increased NK cell activity, but results were not consistent in every patient. Coriolus mushroom and antigen-infused dialyzable bovine colostrum/whey extract did not consistently or significantly increase NK cell activity. These findings are a concern for a number of reasons. Table 6 shows the average retail price of these supplements per month.
These are expensive prices for patients to pay for products that may not be as beneficial as claimed in advertisements. Advertisments from companies over the internet, in health food stores and in magazines may mislead patients into thinking the product will help their natural killer cells. Doctors may also prescribe these supplements without verifying the product's efficacy.
There is no doubt that coriolus mushroom extracts have a place in the treatment of cancer patients. Numerous human trials have been done and results have shown that coriolus may increase survival rates in cancer patients. (28-30,39) Most studies published in peer-reviewed journals, however, have been done on Krestin, protein-bound polysaccharide K, extracted from the mycelia of coriolus versicolor, not on other brands. Krestin is also the only extract of coriolus listed on medline which has been shown to increase NK cell activity in cancer patients. (40) Other manufacturers of coriolus often transfer the results found in Krestin research onto their product even though the two forms of coriolus are not identical. A coriolus extract other than Krestin was used in this study to confirm product efficacy and to verify claims made by the manufacturer.
Shortcomings of this study were as follows: Sample size was small in each group, but represented 29 cancer patients with abnormally low NK cell activities (<20 lytic units) who needed a reliable product to help them. Many patients were taking other nutritional supplements and/or chemotherapy on the same days as the test products. It is possible that these other substances could have interfered with the results. In the clinical world, however, cancer patients are rarely on one medication or nutritional supplement. Because of the complexities of cancer, it is most effectively treated with combination therapy that addresses growth factors, angiogenesis and cellular replication as well as the immune system. A good NK cell activator needs to be able to work even in the midst of other therapies. The only product that consistently increased NK cell activity despite the use of multiple nutritional supplements and concurrent chemotherapy was AHCC.
The dose of antigen-infused dialyzable bovine colostrum/whey extract used in this study was lower than the 600-800mg/day recommended by Stoff. (32) Some manufacturers of this product, however, recommend 100mg/day of antigen-infused dialyzable bovine colostrum/whey extract in conjunction with astragalus, maitake and arabinogalactan, which will support healthy natural killer cell levels. The dose used in this study, therefore, was chosen to lie in between these two recommendations.
NK cell activity can be affected by a variety of factors including depression, lack of social support, (41) high fat diets (>20% of total calories, including unsaturated fats), (42) age and exercise levels. (43) Patients in this study, however, kept their diet and exercise routines consistent. Everyone also had a good support system and did not suffer from major depression.
Critics may say that the NK cell activity is not reliable because it frequently fluctuates. This statement, to the author's knowledge, has not been verified by any published clinical studies. In fact, many studies show that the standard 4-hr [.sup.51]Cr-release assay is very accurate as long it is done properly and the data is expressed appropriately. (44) Critics may also say that the activities of NK cells in an assay are different from their activities in the human body. Numerous clinical studies, however, show there is a relationship between the 4-hr [.sup.51]Cr-release NK cell assay and prognosis, tumor burden and risk of metastasis in cancer patients. (3-22)
Three other products touted as NK cell activators, inositol hexaphosphate with inositol, maitake extract and larch arabinogalactan, were not used in this study for the following reason. Other patients not included in this study were taking these products consistently for several months before baseline NK cell activities were done. These patients happened to have extremely low NK cell activities at baseline despite taking the suggested doses of inositol hexaphosphate with inositol, maitake extract or larch arabinogalactan for several months.
Conclusion
Despite today's advances in oncology, many people with early stage cancers are dying in less than five years. Clearly, advances need to be made in cancer therapeutics. Activating natural killer cells with an oral agent may be one therapy that can improve these survival rates. (28-30, 40, 45) This study found only AHCC to be a consistent natural killer cell activator even when combined with chemotherapy and other nutritional supplements. More studies, however, need to be done to see if AHCC is effective at decreasing recurrence rates and increasing survival rates in early stage cancer patients in remission. The author knows of only one study so far looking at AHCC and prognosis that has been published. This study found that AHCC improved survival rates in postoperative hepatocellular carcinoma patients. This study, however, was not randomized and therefore, results may have been influenced by self-selection bias. (45) Krestin is also another product that shows a lot of promise. Follow-up immune system testing, however, should be done if one is using Krestin or another coriolus product.
In conclusion, all doctors should monitor NK cell activity whenever prescribing a product claiming to be a natural killer cell stimulant even if it is AHCC. Increasing NK cell activity may improve a cancer patient's prognosis. The study author has used this test over and over and has to date, never seen an early stage cancer patient in remission have a recurrence if their NK cell activity was normalized.
Table 1: 1995-2000 5-Year Survival Rates (%) of Conventionally-Treated
Cancer Patients
Type of Cancer Localized Regional Distant
Melanoma 97.6 60.3 16.2
Breast 97.5 80.4 25.5
Bladder 94.1 48.8 5.5
Ovarian 93.5 68.8 28.5
Kidney 91.1 59.1 9.3
Colorectal 89.9 67.3 9.6
Oral Cavity & Pharynx 81.0 50.7 29.5
Non Small Cell Lung Cancer 51.3 17.0 2.2
Small Cell Lung Cancer 21.4 10.8 2.1
Pancreas 15.2 6.8 1.8
Table 2: Effects of Modified Arabinoxylane on NK Cell Activity in Cancer
Patients (Group A)
Concurrent
Age Sex Cancer Type & Stage Chemotherapy Before After
48 [female] Breast Cancer, Stage IV Yes 8.0 5.6
58 [female] Hodgkins Disease, Stage IIA Yes 26.9 11
49 [female] Breast Cancer, Stage I No 8.2 4
41 [female] Breast Cancer, Stage 0 No 14.6 13.4
47 [female] Breast Cancer, Stage I No 24.2 27.9
48 [male] CLL, Stage I No 7.3 9.5
37 [male] NSCLC, Stage IIIA Yes 5.5 15.1
71 [male] Prostate Cancer, Stage IV No 21.2 24
75 [female] ALL w/ Brain Metastases Yes 9.2 20
64 [female] Breast Cancer, Stage I No 10.6 11
39 [male] Liposarcoma, Stage IV Yes 5.0 5.7
75 [male] Glioblastoma multiforme Yes 2.6 13.2
49 [female] Breast Cancer, Stage IIB Yes 8.0 29.6
50 [female] Ovarian Cancer, Stage IV Yes 4.2 22.2
47 [female] Breast Cancer, Stage IIB Yes 5.0 20.1
Mean 10.70 15.49
SD 7.58 8.12
Age Sex Cancer Type & Stage Difference # of Weeks
48 [female] Breast Cancer, Stage IV -2.4 28
58 [female] Hodgkins Disease, Stage IIA -15.9 5
49 [female] Breast Cancer, Stage I -4.2 50
41 [female] Breast Cancer, Stage 0 -1.2 4
47 [female] Breast Cancer, Stage I 3.7 8
48 [male] CLL, Stage I 2.2 25
37 [male] NSCLC, Stage IIIA 9.6 14
71 [male] Prostate Cancer, Stage IV 2.8 35
75 [female] ALL w/ Brain Metastases 10.8 5.5
64 [female] Breast Cancer, Stage I 0.4 8
39 [male] Liposarcoma, Stage IV 0.7 8
75 [male] Glioblastoma multiforme 10.6 6
49 [female] Breast Cancer, Stage IIB 21.6 14
50 [female] Ovarian Cancer, Stage IV 18 8
47 [female] Breast Cancer, Stage IIB 15.1 6
Mean 4.79* 15
SD 9.64
*P<0.10
Table 3: Effects of Coriolus Mushroom on NK Cell Activity in Cancer
Patients (Group B)
Cancer Type Concurrent
Age Sex & Stage Chemotherapy Before After
52 [female] Breast Cancer, No 11.8 8.8
Stage IIB
72 [female] Breast Cancer, No 22.6 18.4
Stage I
47 [female] Breast Cancer, No 6.5 5.0
Stage IIB
55 [male] Bladder No 17.7 12.1
Cancer, Stage II
49 [female] Breast Cancer, No 9.2 12.7
Stage I
41 [female] Breast Cancer, No 13.8 14.6
Stage 0
72 [female] Non-Hodgkins, No 14.2 17.1
Stage I
47 [female] Breast Cancer, No 8.2 9.7
Stage I
Mean 13.00 12.30
SD 5.31 4.44
Cancer Type
Age Sex & Stage Difference # of Weeks
52 [female] Breast Cancer, -3.0 4
Stage IIB
72 [female] Breast Cancer, -4.2 12
Stage I
47 [female] Breast Cancer, -1.5 4
Stage IIB
55 [male] Bladder -5.6 9
Cancer, Stage II
49 [female] Breast Cancer, 3.5 9
Stage I
41 [female] Breast Cancer, 0.8 8
Stage 0
72 [female] Non-Hodgkins, 2.9 19
Stage I
47 [female] Breast Cancer, 1.5 5
Stage I
Mean -0.70* 9
SD 3.38
*Not significant
Table 4: Effects of Antigen-Infused Dialyzable Bovine Colostrum/Whey
Extract on NK Cell Activity in Cancer Patients (Group C)
Cancer Type Concurrent
Age Sex & Stage Chemotherapy Before After Difference
58 [female] Hodgkins Yes 11.0 70 -4.0
Disease,
Stage IIA
52 [female] Breast Yes 8.8 10.2 1.4
Cancer,
Stage IIB
47 [female] Breast No 13.1 6.5 -6.6
Cancer,
Stage IIB
Mean 10.97 7.90 -3.07*
SD 2.15 2.01 4.08
Cancer Type
Age Sex & Stage # of Weeks
58 [female] Hodgkins 4
Disease,
Stage IIA
52 [female] Breast 20
Cancer,
Stage IIB
47 [female] Breast 7
Cancer,
Stage IIB
Mean 10
SD
*Not significant
Table 5: Effects of AHCC on NK Cell Activity in Cancer Patients (Group
D)
Cancer Type & Concurrent
Age Sex Stage Chemotherapy Before After
41 [male] NSCLC, Yes 2.9 13.6
Stage IV
2 [female] Rhabdomyosarcoma, Yes 8.4 25.4
Stage IV
70 [female] Breast Cancer, Stage I No 14.7 57.6
47 [female] Breast Cancer, Stage I No 9.7 16.8
58 [female] Hodgkins Disease, Yes 7 14.4
Stage IIA
53 [female] Desmoid Tumor, Yes 22.3 41.8
Stage I
61 [male] Leiomyosarcoma, Yes 11.4 18.9
Stage IV
47 [female] Breast Cancer, Stage Yes 16.2 42.4
IV
Mean 11.58 28.86
SD 6.05 16.37
Cancer Type &
Age Sex Stage Difference # of Weeks
41 [male] NSCLC, 10.7 7
Stage IV
2 [female] Rhabdomyosarcoma, 17 14
Stage IV
70 [female] Breast Cancer, Stage I 42.9 3
47 [female] Breast Cancer, Stage I 7.1 4
58 [female] Hodgkins Disease, 7.4 6
Stage IIA
53 [female] Desmoid Tumor, 19.5 8
Stage I
61 [male] Leiomyosarcoma, 7.5 11
Stage IV
47 [female] Breast Cancer, Stage 26.2 11
IV
Mean 17.29* 8
SD 12.43
*P<0.01
Table 6: Average Monthly Retail Cost of Four Dietary Supplements for the
Immune System
Antigen-Infused
Dialyzable
Modified Bovine Colostrum/
Arabinogalactan Coriolus Whey Extract AHCC
Dose: 1g/day: 208.50 6g/day: 99.80 400mg/day: 264 3g/day: 300
Cost ($) 3g/day: 625.50 6g/day: 600
References
1. http://seer.cancer.gov/cgi-bin/csr/1975_2001/search.pl
2. Wu J. et al. 2003. Natural Killer Cells and Cancer. Adv Cancer Res. 90:127-56
3. Tratkiewicz JA, Szer J. 1990. Loss of natural killer activity as an indicator of relapse in acute leukaemia. Clin Exp Immunol. May;80(2):241-6.
4. Sorskaar D, Lie SO, Forre O. 1985. Natural killer cell activity of peripheral blood and bone marrow mononuclear cells from patients with childhood acute lymphoblastic leukemia. Acta Paediatr Scand. May;74(3):433-7.
5. Sorskaar D, Forre O, Stavem P. 1988. Natural killer cells in chronic leukemia. Function and markers. Int Arch Allergy Appl Immunol. 87(2):159-64.
6. Schantz SP, et al. 1987. Evidence for the role of natural immunity in the control of metastatic spread of head and neck cancer. Cancer Immunol Immunother. 25(2):141-8.
7. Schantz SP, Campbell BH, Guillamondegui OM. 1986. Pharyngeal carcinoma and natural killer cell activity. Am J Surg. Oct; 152(4):467-74.
8. Sephton SE, Sapolsky RM, Kraemer HC, Spiegel D. 2000. Diurnal cortisol rhythm as a predictor of breast cancer survival. J Natl Cancer Inst. Jun 21;92(12):994-1000.
9. Garzetti GG et al. 1995. Natural killer cell activity in patients with invasive cervical carcinoma: importance of a longitudinal evaluation in follow-up. Gynecol Obstet Invest. 40(2):133-8.
10. Taketomi A et al. 1998. Natural killer cell activity in patients with hepatocellular carcinoma: a new prognostic indicator after hepatectomy. Cancer. 1998 Jul 1;83(1):58-63.
11. Ortac R, Aktas S, Diniz G, Erbay A, Vergin C. 2002. Prognostic role of natural killer cells in pediatric mixed cellularity and nodular sclerosing Hodgkin's disease. Anal Quant Cytol Histol. Oct;24(5):249-53.
12. Tajima F. et al. 1996. Natural Killer Cell Activity and Cytokine Production as Prognostic Factors in Adult Acute Leukemia. Leukemia. Mar;10(3):478-82
13. Ogata H. et al. 1989. A clinical study of a multiregression analysis on the NK activity and related clinical factors in patients with lung cancer. Gan No Rinsho. 1989 Apr;35(5):554-9.
14. Fujisawa T, Yamaguchi Y. 1997. Autologous tumor killing activity as a prognostic factor in primary resected nonsmall cell carcinoma of the lung. Cancer. Feb 1;79(3):474-81.
15. Cosiski Marana HR, Santana da Silva J, Moreira de Andrade J. 2000. NK cell activity in the presence of IL-12 is a prognostic assay to neoadjuvant chemotherapy in cervical cancer. Gynecol Oncol. Sep;78(3 Pt 1):318-23.
16. Aparicio-Pages MN, Verspaget HW, Pena AS, Lamers CB. 1991. Natural killer cell activity in patients with adenocarcinoma in the upper gastrointestinal tract. J Clin Lab Immunol. May;35(1):27-32.
17. Yang YB. 1990. Detection of natural killer cells activity in patients with laryngeal carcinoma using the 51Cr release assay. Zhonghua Er Bi Yan Hou Ke Za Zhi. 1990;25(1):42-4, 63.
18. Apostolopoulos A, Symeonidis A, Zoumbos N. 1990. Prognostic significance of immune function parameters in patients with chronic lymphocytic leukaemia. Eur J Haematol. Jan;44(1):39-44.
19. Garzetti GG, Cignitti M, Ciavattini A, Fabris N, Romanini C. 1993. Natural killer cell activity and progression-free survival in ovarian cancer. Gynecol Obstet Invest. 35(2):118-20.
20. Gallego-Melcon S, Espanol Boren T, Sanchez de Toledo J. Prats Vinas J. 1991. Natural killer cell function in children with malignant solid neoplasias. Med Pediatr Oncol. 19(3):175-81.
21. Levy S. et al. 1987. Correlation of Stress Factors with Sustained Depression of Natural Killer Cell Activity and Predicted Prognosis in Patients with Breast Cancer. J Clin Oncol 5:348-353.
22. Tartter PI, et al. 1987. The Prognostic Significance of Natural Killer Cytotoxicity in Patients With Colorectal Cancer. Arch Surg 1987;122:1264-1268
23. Kimura H, Yamaguchi Y. 1997. A phase III randomized study of interleukin-2 lymphokine-activated killer cell immunotherapy combined with chemotherapy or radiotherapy after curative or noncurative resection of primary lung carcinoma. Cancer. 1997 Jul 1;80(1):42-9.
24. Semino C, et al. 1999. Adoptive immunotherapy of advanced solid tumors: an eight year clinical experience. Anticancer Res. 1999 Nov-Dec;19(6C):5645-9.
25. Yamashita N. et al. 1986. Inhibition of Natural Killer Cell Activity of Human Lymphocytes by Eicosapentaenoic Acid. Biochem Biophys Res Comm 138, 3, 1058-1067.
26. McHugh MI et al. 1977. Immunosuppression with Polyunsaturated Fatty Acids in Renal Transplantation 24, 4, 263-267
27. Ghoneum M. 1998. Enhancement of Natural Killer Cell Activity by Modified Arabinoxylane from Rice Bran (MGN-3). Int J Immunotherapy XIV (2), 89-99.
28. Kudo S, et al 2002. Effectiveness of immunochemotherapy with PSK, a protein-bound polysaccharide, in colorectal cancer and changes of tumor marker. Oncol Rep 9(3):635-8.
29. Ohwada S, et al. 2004. Adjuvant immunochemotherapy with oral Tegafur/Uracil plus PSK in patients with stage II or III colorectal cancer: a randomised controlled study British Journal of Cancer 90, 1003-1010.
30. Iino Y, Yokoe T, Maemura M, Horiguchi J, Takei H, Ohwada S, Morishita Y. 1995. Immunochemotherapies versus chemotherapy as adjuvant treatment after curative resection of operable breast cancer. Anticancer Res Nov-Dec;15(6B):2907-11
31. http://www.nuskin.com/canada/images/pdf/aie10_brief.pdf
32. Stoff JA. Antigen Infused Dialyzable Bovine Colostrum/Whey Extract. Insight Consulting Services, 2000.
33. Ghoneum M, et al. 1995. Immunomodulatory and Anticancer Effects of Active Hemicellulose Compound (AHCC). Int J Immunotherapy XI (1) 23-28.
34. Vojdani A, Thrasher JD. 2004. Cellular and Humoral Immune Abnormalities in Gulf War Veterans. Environ Health Perspect 112:840-846.
35. Whiteside TL, Bryant J, Day R, Herbernann RB. 1990. Natural killer cytotoxicity in the diagnosis of immune dysfunction: criteria for a reproducible assay. J Clin Lab Anal 4: 102-110.
36. Strayer DR. et al. 1984. Low natural cytotoxicity of peripheral blood mononuclear cells in individuals with high familial incidences of cancer. Cancer Res. Jan;44(1):370-4.
37. Nakajima T. et al. 1987. Relationship between natural killer activity and development of hepatocellular carcinoma in patients with cirrhosis of the liver. Jpn J Clin Oncol. Dec;17(4):327-32.
38. Imai K, et al. 2000. Natural Cytotoxic Activity of Peripheral Blood Lymphocytes and Cancer Incidence: an 11-Year Follow-Up Study of a General Population. Lancet. 356. 1795-99
39. Torisu M, et al. 1990. Significant prolongation of disease-free period gained by oral polysaccharide K (PSK) administration after curative surgical operation of colorectal cancer. Cancerlmmunol Immunother 31: 261-268.
40. Chou CY, Hsieh CY, Chen CA, Hsieh KH. 1990. Enhanced natural killer cell activity in patients with cervical carcinoma by postoperative PS-K immunotherapy. J Formos Med Assoc. Jun; 89(6): 461-5.
41. Levy S. et al. 1987. Correlation of Stress Factors with Sustained Depression of Natural Killer Cell Activity and Predicted Prognosis in Patients with Breast Cancer. J Clin Oncol 5: 348-353.
42. Barone J, et al. 1989. Dietary Fat and Natural Killer Cell Activity. Am J Clin Nutr 50: 861-7.
43. Fiatarone MA, et al. 1989. The Effect of Exercise on Natural Killer Cell Activity in Young and Old Subjects. J Gerontol 44, M37-45)
44. Pross HF et al. CH1-Assays for NK Cell Cytoxicity-Their Values and Pitfalls. In: Lotzova E, Herberman RB, eds. Immunobiology of Natural Killer Cells. Vol 1. Boca Raton, FL: CRC Press, 1986.
45. Matsui Y. et al. 2002. Improved prognosis of postoperative hepatocellular carcinoma patients when treated with functional foods: a prospective cohort study. J Hepatol. Jul;37(1):78-86.
by James Belanger, ND, MT
About the author: James T. Belanger, ND received his BS from the University of Massachusetts and his ND from Bastyr University. He is the secretary of the Massachusetts Society of Naturopathic Doctors and the treasurer of the Oncology Association of Naturopathic Physicians. In addition to his private practice in Lexington, Massachusetts, he currently teaches nutrition at the New England School of Acupuncture. After surviving cancer himself, Dr. Belanger has studied oncology research in depth and has created a center in Lexington, Massachusetts, along with his wife Dr. Karen Braga, which focuses on the holistic care of people with cancer.
Copyright: Lexington Natural Health Center, Dr. James T. Belanger
Correspondence:
Dr. James T. Belanger
Lexington Natural Health Center
442 Marrett Rd, Suite 8
Lexington, Massachusetts 02421 USA
781-274-6190
www.lexingtonnaturalhealth.com
COPYRIGHT 2005 The Townsend Letter Group
COPYRIGHT 2005 Gale Group