Hiroiku Ueno, M.D. / President of Asahi Alternative Clinic

Relapse After Cancer Surgery

None

Beta Glucan

1. Introduction

It has been already shown that malnutrition makes patients susceptible and vulnerable to infection. As the immune system has become better understood and analyzed in details, the relevance between nutrition and immune state has been found to be more important than we had expected. Nutrition is involved in aging, allergy and host defense, as well as cancer and infection. Therefore, it is important that the various aspects of nutrition be considered in the treatment of each patient. We have seen many patients suffering from disorders such infections, cancer, hematological disorders, aging, chemotherapy, surgery, radiation, et cetera, who have a compromised immune system which is partially the result of malnutrition. It is important, therefore, that in patients with a compromised immune system, the improvement of immune function be a priority.

2. Methods

The effect of beta-1,3-D-glucan* (beta glucan) on the rate of cancer relapse was assessed in 49 post-surgical patients (breast cancer: 19, ovarian cancer: 8, cervical cancer: 22). All the patients were clinically evaluated with stage 2 cancer. Beta glucan was administered to 26 patients for seven days before and for 15 months after surgery. Each patient was treated with one capsule of beta glucan (2.5 mg/capsule) orally one hour before meals, three times a day; 23 received no treatment and served as controls.

In a second trial the effect of beta glucan on the survival of cancer patients was assessed in 99 post-surgical patients that had suffered relapse, were inoperable and were given 3 months or less to live. 54 of these patients were treated with 2 capsules of beta glucan three times a day (total dose of 15 mg/day) and 45 were not treated and served as controls. The beta glucan used in the studies above was purified from baker's yeast and manufactured by Immudyne (USA) [sold in Japan under the trademark of MacroForce]

3. Results

In the first trial a comparison of two groups showed that after surgery 5 patients out of 23 suffered relapse in the control group.

No relapse occurred in the patients treated with beta glucan during a 15-month follow-up (Table 1). Table 2 shows the time

course of relapse during the 15-month follow-up. The beta glucan-treated group has now been followed for 20 months without any reoccurrence.

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*The beta 1,3-D-glucan used in this study and manufactured by Immudyne is actually Beta-1,3/1,6-D-glucan. It is referred to

as Beta-1,3-D-glucan because of the small amounts (3-8%) of beta (1®6) bonds it contains. However, it is the small number of (1-6) bonds that confer biological activity to the molecule.

Table 1

Effect of Beta-1,3-D-Glucan on

Treatment

Cancer Type

# Patients

# Relapses

Breast Stage II

Ovarian Stage II

Cervical Stage II

2 (8.7%)

3 (13%)

Time After Surgery (Months)

Beta Glucan

Beta Glucan

Breast Stage II

Ovarian Stage II

Cervical Stage II

Table 2

Effect of beta-1,3-D-Glucan on Cancer Recurrence After Surgery

In the second trial 65% (35/54) of the patients who received beta glucan survived more than 3 months and 43% (23/54) survived more than 6 months. In contrast, only 4.4% (2/45) of the untreated, control patients survived 3 months and none survived 6 months (Table 3).

Table 3

Effect of Beta-1,3-D- Glucan on

Survival of Terminal Patients

Treatment	# Patients	Patients Surviving
None	45	3 Mo.	6 Mo.
		2 (4.4%)	0
Beta Glucan	54	35 (65%)	23 (43%)

4. Discussion

The anitviral, antitumor, anti-immaflatory effect, and macrophage activation activities of beta glucan have already been reported. Investigators in the United States have reported that macrophages have the receptor for beta-glucan, and that the binding of beta glucan to the receptor leads to the activation of macrophage. Subsequently, other immune cells such as neutrophils, NK cells, and B cell have been found to have the receptor and are activated by beta-glucan. Activated macrophages release IL-1, IL-12, IFN-gamma and a number of other cytokines that are involved in the activation of helper T cells. The phagocytosis of apoptotic cancer cells allows macrophages to present the cancer antigens to naive T cells (TO cells), the information is then conveyed

Table 4

Effect of beta glucan on Immune Markers (a) and Tumor Markers (b) of a 48-year old woman with breast cancer Stage 1

4a Immune Markers

Immune Markers	Before	1 Month	2 Months	3 Months
TNFg (14)	4.0	17.2	23.9	45.2
IL-12 (7.8)	8.7	15.4	24.2	41.5
NK cells (18-40)	15	22	26	64
LAK (20-80)	19	58	72	84
CD161	8.2	12.1	19.2	18.51
Three-color IFNg/IL-4(7)	0.27 4/14.7	1.61 17.2/10.7	19.9 23.9/1.2	41.1 45.2/1.1

4b. Tumor Markers

Tumor Markers	Before	1 Month	2 Months	3 Months
BCA 225 (160)	130	98	83