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Ganoderma lucidum Spore Induced CA72-4 Elevation in Gastrointestinal Cancer: A Five-Case Report
Bing Yan, Xianze Meng, Jun Shi, Zhifeng Qin, Pinkang Wei and Lixing Lao
Integr Cancer Ther 2014 13: 161 originally published online 25 November 2013
DOI: 10.1177/1534735413510022
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ICTXXX10.1177/1534735413510022Integrative Cancer TherapiesYan et al

Article

Ganoderma lucidum Spore Induced CA72-4

Elevation in Gastrointestinal Cancer: A
Five-Case Report

Integrative Cancer Therapies

2014, Vol. 13(2) 161166
The Author(s) 2013
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DOI: 10.1177/1534735413510022
ict.sagepub.com

Bing Yan, PhD1, Xianze Meng, PhD1, Jun Shi, PhD1, Zhifeng Qin, MD1, Pinkang
Wei, MD1, and Lixing Lao, MD2

Abstract
Ganoderma lucidum spore (GLS), an over-the-counter herbal supplement, is widely used by cancer patients in China.
Although preclinical studies have shown it to be safe, complete safety data on GLS is still lacking. In this article, we report 5
cases of gastrointestinal cancer that were treated with GLS plus multiple strategies between 2010 and 2011. These patients
presented with increased levels of the serum tumor marker CA72-4, one of the most valuable markers for monitoring
therapeutic response in patients receiving gastrointestinal cancer treatment, after oral ingestion of GLS twice a day for 1
or 2 months. Interestingly, CA72-4 rapidly returned to normal levels when the patients discontinued the supplement and
no change in clinical symptoms accompanied the CA72-4 surge. Taking into consideration that the underlying mechanism
of this reaction is obscure, we suggest that additional studies are urgently needed and GLS be used with caution in cancer
patients.
Keywords
gastrointestinal cancer, CA72-4, alternative medicine, Ganoderma lucidum spore, case report

Introduction
Due to the limitations of conventional cancer treatment,
large numbers of cancer patients turn to complementary and
alternative medicine,1,2 most commonly traditional Chinese
medicine (TCM).3 Ganoderma lucidum (Figure 1A), also
known as Lingzhi or Reishi, is a species of basidiomycete. It
was recorded in the oldest Chinese materia medica,
Classical Pharmacopeia of the Heavenly Husbandman
(206 BC-8 AD) and has been used in China for more than
2000 years.4 It is well known as the mushroom of immortality, widely used in China and many Asian countries to
promote longevity, maintain vitality, and treat multiple diseases, including gastrointestinal cancer.5-8 Since the 1980s,
its anticancer properties, such as cytotoxicity, immunomodulation, and the ability to suppress angiogenesis and induce
apoptosis, have been investigated.7-10
As an over-the-counter supplement, this fungus has been
commercially processed into many products,11,12 one of
which, Ganoderma lucidum spore (GLS; Figure 1B), is
becoming increasingly popular among cancer patients in
Asian countries.13,14 Clinical observations of GLS have
shown that it may be effective in treating gastrointestinal
cancer with few adverse effects15: animal studies demonstrate that long-term toxicity in rats only occurs at dosages
higher than 5.40 g/kg, which corresponds to 60 times of the

clinical human dosage.16 However, the clinical safety evaluation of this remedy is far from sufficient.
In the current report, we describe 5 cases of gastrointestinal cancer. Each of these patients presented with a surge of
the serum tumor marker CA72-4 after taking GLS; however, no disease progression was observed. Although the
underlying mechanism of this reaction is obscure, our cases
indicate that additional studies are urgently needed since a
consistent rise of CA72-4 is generally thought to be indicative of disease progression17,18 and physicians would conventionally shift the treatment for these patients.
All GLS administered to these patients was processed
using standard quality controls with a composition ratio of
1:4 of Ganoderma lucidum sporophore and broken GLS.
The high performance liquid chromatograms (HPLC) of the
samples are shown in Figure 2.

Second Military Medical University, Shanghai, China

University of Maryland, Baltimore, MD, USA

Corresponding Author:
Zhifeng Qin, Department of Traditional Chinese Medicine, Shanghai
Changzheng Hospital, Second Military Medical University, 415 Fengyang
Road, Shanghai 200003, China.
Email: yanbing3741@gmail.com

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Integrative Cancer Therapies 13(2)

splenectomy, he underwent 5 cycles of chemotherapy. The
response was good; only his CEA value was greater than the
reference level, and it trended toward the normal range. He
then presented in our department to obtain the alternative
treatment -elemene,20,21 which was a naturally occurring
compound isolated from the TCM herb Curcumae Radix22
and began using 1.8 g of GLS a day as a dietary supplement
(-elemene was not stopped in the subsequent treatment).
His CA72-4 level immediately surged to 99.23 U/mL; it fell
back into the normal range a month after the GLS was
stopped (Figure 3B). He visited our department for 8 more
months, during which we detected no progression of the
disease. During the treatment, his liver function indexes
remained normal.

Case 3
Figure 1. Fruiting body of Ganoderma lucidum (A) and
Ganoderma lucidum spore (B).

Case Reports
Case 1
A 64-year-old man was diagnosed in 2010 with gastric adenocarcinoma (Table 1). After a distal subtotal gastrectomy,
he underwent 5 one-month cycles of chemotherapy. He
responded to treatment for only 4 months before carcinoembryonic antigen (CEA) and CA72-4 levels began to rise (reference values = 0-5 g/mL and 0-8.2 U/mL, respectively).
Along with a new chemotherapy regimen, he began taking 6
capsules (1.8 g) of GLS a day as a dietary supplement. One
month later, when the CA72-4 had surged to 126.30 U/mL
and the CEA was still rising, we suggested that he stop the
GLS and try an alternative herbal medicine, Hua Chansu, a
Chinese medicine that comes from dried toad venom from
the skin glands of Bufo gargarizans or Bufo melanostictus,
which was commonly used to treat gastrointestinal cancer.19
After 2 cycles of treatment, the CA72-4 values fell into the
normal range. He began taking GLS again; a month later, the
CA72-4 had sharply risen to 435.78 U/mL, so the supplement was stopped. When he came to our department for
follow-up 1 month later, CA72-4 levels had returned to normal and the CEA level had decreased (Figure 3A). An
enhanced computed tomography scan of the abdomen 6
months after the last CA72-4 surge showed no progression
of the disease. During the treatment, his liver function
indexes all remained within the normal range.

Case 2
A 77-year-old man was diagnosed in 2010 with gastric adenocarcinoma (Table 1). After a total gastrectomy and

A 61-year-old woman was diagnosed in 2009 with gastric

adenocarcinoma (Table 1). After a radical proximal gastrectomy and gallbladder resection, she responded to chemotherapy for only 4 months before her CEA and CA72-4 levels
began to rise. We recommended an alternative herbal medicine, Xiao Aiping, a Chinese medicine that comes from
Glaucescent Fissistigma Root, which was frequently used for
gastrointestinal cancer in China.23 After 3 cycles of treatment,
the CEA value had increased to 54.51 g/L, but the CA72-4
had declined to normal. She then took GLS as dietary supplement along with the Xiao Aiping, which was continuously
applied in the subsequent treatment. A month later, the
CA72-4 had surged to 99.92 U/mL and the CEA to 60.83
g/L. Dramatically, both the CA72-4 and CEA dropped
sharply by the next month without any change in treatment.
The GLS was then withdrawn, and the CEA and CA72-4 both
rapidly fell into the normal range (Figure 3C). Ten months
later, when she visited our department for follow-up, we
detected no progression in her disease. During the treatment,
her liver function indexes remained within the normal range.

Case 4
A 56-year-old man was diagnosed in 2008 with anastomotic
gastric adenocarcinoma (Table 1). Initially, he used Hua
Chansu19 as a treatment. Serum tumor markers were monitored every month; after 24 one-month cycles of treatment,
CEA and CA72-4 were normal, as was liver function. He
then took GLS as a dietary supplement accompanied with
Hua Chansu. The CA72-4 titer increased sharply to 562.30
U/mL by the 1-month follow up; it decreased rapidly to
27.65 U/mL 2 months after withdrawal of the GLS.
Throughout this period, the CEA only showed small
changes (Figure 3D). The patient was followed by our
department for 8t more months, during which we detected
no progression of his disease. During treatment, his liver
function remained normal.

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Yan et al

Figure 2. HPLC-DAD of the sample. Samples were randomly tested 10 times, and the absorbance was at 280 nm.

Figure 3. Multiples of the measured values of CA72-4 and CEA compared to their respective reference values at various treatment stages.

Case 5
A 59-year-old woman was diagnosed in 2010 with colorectal cancer (Table 1). After radical surgery, she responded to

chemotherapy for 6 months before her CEA levels began to

rise. She stopped chemotherapy and began Xiao Aiping23
plus 1.8 g of GLS a day (Xiao Aiping was not ceased in the
subsequent treatment). Her CA72-4 had surged to 287.10

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Integrative Cancer Therapies 13(2)

Table 1. Clinical Pathology of the 5 Patients.

CA72-4 Values Associated With GLS (U/mL)
Patient

Gender

Age

Disease

Stagea

Beforeb

Duringc

Afterd

1
2
3
4
5

Male
Male
Female
Male
Female

64
77
61
56
59

GA
GA
GA
GA
CA

T3N1M0
T4bN1M0
T4bN0M0
e
T2N0M0

65.07
7.75
8.09
12.88
3.18

435.78
99.23
99.92
562.30
287.10

5.52
1.84
8.81
27.65
7.76

Abbreviations: GLS, Ganoderma lucidum spore; GA: gastric adenocarcinoma; CA: colorectal cancer; AJCC, American Joint Committee on Cancer.
a
The stages follow AJCC gastric cancer guidelines (2010, 7th version).
b
The last CA72-4 value detected before the first use of GLS.
c
Peak value of CA72-4 during GLS treatment.
d
The CA72-4 value of Patient 4 was obtained 2 months after GLS was discontinued; the other patients values were taken 1 month after discontinuation of
the supplement.
e
Anastomotic gastric adenocarcinoma, not applicable to the AJCC staging system.

U/mL 1 month later, and her CEA had risen slightly. She
stopped the GLS. Her CA72-4 immediately returned to normal, and her CEA also became normal after 2 months
(Figure 3E). Our department followed her for 9 months,
during which an enhanced abdominal computed tomography scan detected no progression of the disease. During
treatment, her liver function remained normal.

Discussion
With herbal therapies becoming increasingly popular
among cancer patients, it is important for physicians to recognize the effects of such therapy in their patients since the
majority of these agents are commonly not subjected to premarket toxicity examination to test their safety or efficacy.24,25 As shown in Figure 2, all 5 gastrointestinal cancer
patients experienced a surge of the serum tumor marker
CA72-4 after taking GLS. Except in Case 3, the supplement
was withdrawn immediately when their CA72-4 levels
surged, after which their levels decreased sharply to reference levels. Interestingly, in Case 3, the only patient who
kept using GLS after her CA72-4 level peaked, CA72-4
also sharply decreased after an initial month of increase.
Additionally, although 1 patient experienced a surge in
CEA along with the rise in CA72-4, the patients showed no
significant change in clinical symptoms, and in follow-up
we found no progression in disease. These data demonstrate
that GLS, alone or combined with other agents, may induce
the elevation of CA72-4. However, this elevation may not
correlate with disease progression.
Our cases do highlight concerns regarding the safety of
GLS. GLS is an herbal remedy containing multiple constituents, not all of which have been identified. However, the
preparation is known to contain major bioactive components such as ergosterol, triterpenoids, unsaturated fatty
acids, and polysaccharides,12,26-28 all of which are generally

believed to be safe. Furthermore, in animal studies the

LD50 of GLS has been shown to be more than 10.0 g/kg
with no mutagenic or teratogenic action, which suggests
that GLS is probably safe.29
CA72-4 is one of the most valuable markers for monitoring response to treatment in gastric cancer patients30-34 and
that an increase in level of this tumor marker may invariably heralds disease progression; however, the phenomenon
of tumor marker surge during treatment is registered in
some special conditions, which should catch our attention.
Previous studies report that cytotoxic drugs can induce a
surge in serum tumor markers. For example, Srbye and
Dahl report a transient CEA increase at the start of oxaliplatin combination therapy for metastatic colorectal cancer;
the CEA levels peaked between 13 and 56 days, and the
median rise from baseline was 263%.35 Loprinzi et al found
a CEA surge in 14 of 29 responding metastatic breast cancer
patients treated with dibromodulcitol, doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) or DAVTH
alternating with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone (CMFP); the mean rise was 243% of
pretreatment CEA levels.36 This phenomenon was commonly interpreted as the result of more powerful chemotherapy agents inducing greater tumor cell lysis. In our Case
3, the only patient who continued GLS for a long period,
CA72-4 surged rapidly when GLS was initiated and then
sharply decreased, as did CEA, without any change in treatment, thus mirroring the aforementioned studies. Taking
into consideration that studies demonstrate that the GLS
extract possesses direct cytotoxic effects on cancer cells
through multiple mechanisms such as apoptosis, cell cycle
arrest, and enhanced cell-mediated immune response,37-40
there is a possibility that the surge of CA72-4 might be due
to GLS-produced tumor cell lysis. However, evidence to
support this hypothesis is lacking as no other clinical symptom improvements accompanied the CA72-4 surge.

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Yan et al
To date, the production mechanism of CA72-4 in cancer
cells is not well illustrated. An additional possibility for the
surge of CA72-4 in our cases is that GLS may directly or
indirectly modulate CA72-4 production without a corresponding promotion of either tumor progression or antitumor effects. In such a scenario, tumor cells may not be
growing while GLS is effectively promoting CA72-4 production. However, we cannot draw clear conclusions based
on the current data.
The history of mushroom use for medicinal purposes
began with TCM more than 5000 years ago, and on most
occasions, these agents are categorized as generally
regarded as safe,8 but a long history of use, traditions,
faith, popularity, and anecdotes cannot always be taken as
evidence for the safety of these agents.41 Although our cases
may indicate that the usage of GLS in gastrointestinal cancer patients be harmless, it cannot be taken as an evidence
for its free application in patients. Rigorous evidence for its
safety or efficacy can only be obtained from randomized
controlled trials in the future.

Conclusion
Our cases suggest that the safety of GLS in cancer patients
should be further studied. GLS should be used with caution, and patients should be carefully monitored and
followed-up.
Acknowledgments
We thank Dr Lyn Lowry of the Center for Integrative Medicine,
University of Maryland School of Medicine, for her editorial
support.

Authors Note
Bing Yan and Xianze Meng contributed equally. Other authors
contributed to language translation, editing, and scientific advice.

Declaration of Conflicting Interests

The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.

Funding
The authors(s) received no financial support for the research,
authorship, and/or publication of this article.

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