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Can maitake MD-fraction aid cancer patients? - Original Research

Alternative Medicine Review , June, 2002 by Noriko Kodama, Kiyoshi
Komuta, Hiroaki Nanba

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Maitake mushroom (Grifola frondosa) MD-fraction containing beta-1,6 glucan
with beta-1,3 branched chains has previously exhibited strong anticancer
activity by increasing immune-competent cell activity. (1,2) In this non-random case
series, a combination of MD-fraction and whole maitake powder was investigated
to determine its effectiveness for 22- to 57-year-old cancer patients in
stages II-IV. Cancer regression or significant symptom improvement was observed in
58.3 percent of liver cancer patients, 68.8 percent of breast cancer
patients, and 62.5 percent of lung cancer patients. The trial found a less than 10-20
percent improvement for leukemia, stomach cancer, and brain cancer patients.
Furthermore, when maitake was taken in addition to chemotherapy,
immune-competent cell activities were enhanced 1.2-1.4 times, compared with chemotherapy
alone. Animal studies have supported the use of maitake MD-fraction for cancer.

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Introduction

Prior to 1980, maitake mushroom was foraged but could not be cultivated in
medium. Since 1981, however, this mushroom has been commercially cultivated in
Japan and elsewhere. Cultivation and development of standardized products, such
as the MD-fraction, have provided opportunities to study its various
medicinal properties: antitumor, (1-5) antidiabetic, (6) antihyperlipoid, (7) and
antihepatitis. (8) There is a growing consensus that maitake MD-fraction strongly
enhances immune-competent cell activities.

Animal Studies

C3H mice bearing MM-46 carcinoma (breast tumor) were given either 0.5 mg/kg
MD-fraction by intraperitoneal (i.p.) injection or 1.0 mg/kg MD-fraction by
oral administration for 10 days. After day 20, solid tumors were extirpated and
weighed to determine the tumor growth inhibition ratio. Tumor regression of
75-85-percent was observed. Treatment with the MD-fraction increased the
activities of natural killer cells, cytotoxic T cells, macrophages, and delayed-type
hypersensitivity T cells by 1.23-2.5 times. The production of interleukin-1
(IL-1) from macrophages and of interleukin-2 (IL-2) from helper T cells was
potentiated by 1.7-3.4 times. From these results the conclusion may be drawn that
the immune-competent cell abilities to inhibit tumor growth were enhanced by
MD-fraction. (1,2)

Doses of 10-50 mg MD-fraction and 250 mg powdered whole maitake containing 5
mg vitamin C were tested to investigate acute and chronic toxicity. Maitake
was administered at a dose of 50 mg MD-fraction to mice i.p. for 50 days. By day
60, 10 days after ceasing treatment, no abnormal liver, kidney, or spleen
tissue was found and blood tests were within normal ranges. These findings
indicate MD-fraction does not appear to be toxic to animals. The toxicity of
powdered whole maitake administered orally was also examined by feeding mice maitake
tablets for 50 days. No toxicity to mouse organs was detected.

Clinical Application

Having concluded that both the MD-fraction and whole maitake tablets were
safe and nontoxic, a non-randomized clinical trial using a combination of
MD-fraction and maitake tablets was conducted to determine its effectiveness for
advanced cancer patients. A total of 36 cancer patients in stages II-IV, from 33
to 68 years old, participated in the trial. The data were collected with the
cooperation of the patients' medical doctors in Japan. Patients were given
tablets containing MD-fraction and whole maitake powder after discontinuing
chemotherapy due to side effects. Cancer regression or significant symptom
improvement was observed in: (1) 11 of 16 breast cancer patients; (2) 7 of 12 liver
cancer patients; and (3) 5 of 8 lung cancer patients.

To judge the effectiveness of the treatments, a positive response was defined
as occurrence of one of the following:

1. The size of the cancer on CT or MRI scanning was reduced 1/2-3/4.

2. The value of the tumor marker was decreased 1/3-1/2.

3. T, N, or M factors were reduced or remained unchanged (Table 1 defines
these factors).

4. The number of immune-competent cells (natural killer cells, macrophages, T
lymphocytes, etc.) was increased to normal levels.

5. The production of cytokine (IL-1 and IL-2) was enhanced.

Case Series

The following cases represent patients with various types of cancer treated
with maitake.

Case History A

A 57-year-old male presented with lung cancer (epidermoid carcinoma). He was
diagnosed as stage IV (any T, any N, [M.sub.1]) but refused chemotherapy. The
first cancer had been diagnosed as colloid carcinoma in 1985. It metastasized
to a lung in April 1989 and presented with 1.5 cm and 3.8 cm cancer foci. At
this time he was administered 100 mg MD-fraction and 6 g whole maitake tablets
daily for five years. He died 60 months later in May 1994. However, his
condition showed an improvement and was diagnosed as stage III-A before he passed
away. After administration of MD-fraction and maitake tablets, both T factor 2
and N factor 2 were observed. The larger cancer was reduced to 3 cm and the
smaller cancer disappeared completely. However, his cancer had metastasized to
the lymph nodes (homolateral mediastinum).
Case History BA 47-year-old female presented with hepatocellular carcinoma,
stage II ([T.sub.1], [N.sub.1], [M.sub.0]). Beginning in March 1994 she was
treated with 80 mg/[m.sup.2] of cisplatin (CDDP) four times daily. In January
1995, however, her treatment was changed to 50 mg MD-fraction and 4 g whole
maitake tablets daily and the cisplatin treatment was discontinued. After 2.5 years
(June 1997), IL-2 production was increased 2.2-fold by maitake
administration. IL-2 from T-helper cells is a reflection of activation of cytotoxic T-cells.
By July 1999 the tumor had completely disappeared.Case History CMore Articles
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A 54-year-old male presented with hepatocellular carcinoma, stage III
([T.sub.3], [N.sub.1], [M.sub.0]). He had been treated with percutaneous ethanol
injection treatment (PEIT) and 20 mg adriamycin (ADM), also by injection, daily
from April 1995 to January 1996. He refused to continue the treatment because of
lack of effectiveness and severe side effects from ADM. He began a regimen of
40 mg MD-fraction and 5 g maitake tablets per day with the PEIT. After one
year, the level of bilirubin was reduced from 3.2 mg/dL to 1.6 mg/dL; albumin
also improved from 3.1 mg/dL to 1.9 mg/dL.Case History DA 45-year-old female
presented with hepatocellular carcinoma stage III ([T.sub.3], [N.sub.1],
[M.sub.0]). Before treatment with maitake, she had a serum bilirubin of 3.2 mg/dL,
albumin of 2.1 mg/dL, and prothrombin activation of 43 percent. She received
transcatheter arterial embolization (TAE) 10 mL lipiodol (iodized poppy seed oil),
15 mg ADM, and 100 mg cisplatin from May 1995, but discontinued in January
1996 at which time she began daily doses of 100 mg MD-fraction and 4 g maitake
tablets daily, along with 100 mg of the chemotherapy drug 5-fluorouracil
(5-FU). As of September 1997, the value of bilirubin was 2.1 and albumin was 3.0,
while prothrombin activation increased to 72.2 percent. Since February 1998 she
has received only maitake products and is now diagnosed as stage I.Case
History EA 56-year-old male presented with hepatocellular carcinoma stage IV,
preceded nine years earlier by lung cancer (epidermoid carcinoma). He had had half
of his left lung surgically removed and begun treatment with chemotherapy; but
in March 1994 a metastatic cancer focus was observed in the liver. The patient
was then administered 150 mg MD-fraction and 6 g whole maitake tablets daily.
In August 1999, the value of IL-2 production was enhanced 1.7-fold and counts
of CD4+ cells were increased 1.3-fold. The tumor, however, remained
unchanged. As of February 2002, there has been no tumor growth or metastasis.Case
History FA 41-year-old female presented with estrogen-receptor positive (ER+)
breast cancer (intraductal carcinoma) stage III ([T.sub.1], [N.sub.1b], [M.sub.0]).
Tumors were measured at 2.4 cm and 0.7 cm in diameter. In September 1996, two
of the solid cancers were surgically removed. The patient then began taking
10 mg of the anti-estrogen tamoxifen (TAM) and 100 mg 5-FU until December 1996.
A cancer metastasis of 1.3 cm, however, was found in a lung in June 1997. The
patient was then administered 125 mg MD-fraction and 4 g whole maitake
tablets daily for 20 months. In March 1999 it was confirmed that the lung tumor had
disappeared. While taking maitake, IL-2 production and CD4+ cell counts were
increased by 1.5 and 1.3 times, respectively. As of early 2002 the tumor had
not reappeared.
ConclusionTable 2 summarizes the immune-potentiating effects of maitake in
cancer patients in this study. Although the data are preliminary, this case
series illustrates the immune-enhancing properties of maitake MD-fraction and
whole powdered maitake. It also appears that maitake may have the potential to
decrease the size of lung, liver, and breast tumors. Further study comparing the
effects of maitake with conventional treatment outcomes seems warranted. For
more information on mechanisms of action and clinical applications of maitake,
see Alternative Medicine Review 2001;6(1):48-60.
Noriko Kodama, PhD--Department of Microbial Chemistry, Kobe Pharmaceutical
UniversityKiyoshi Komuta, MD, PhD Department of Medicine, Osaka Police Hospital,
Kitayamacho, Tennoji-ku, Osaka, Japan.More Articles of Interest
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Hiroaki Nanba, PhD--Department of Microbial Chemistry, Kobe Pharmaceutical
University Correspondence address: Department of Microbial Chemistry, Kobe
Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe
658-8558, Japan

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