Research Results and Mechanism of Action for REISHI – Ganoderma Lucidum – Polysaccharides and Trace Minerals in Radiation Protection
The mechanisms by which Reishi helps pre- and post-exposure to radiation are several:
The glucans, beta-glucans and heteropolysaccharides are all potent immune modulators and anti-tumor agents. They speed the recovery of bone marrow and limit radiological induced blood changes, as well as directly acting to limit the formation of onco-clusters (cancer). They also enhance antibiotics, and other radio-protective drugs.
Natural source bioactive iodine at 1000% daily requirement saturates and protects the thyroid against absorption of radioactive iodine. This is a much a more practical and non-toxic approach than the recommended Potassium Iodate (KI) at 1000 times the daily requirement, and it is neither toxic nor prone to side effects as is the KI. Reishi contains approx 10 x daily requirement in the form of bioavailable iodine chelates and salts. The majority of scientist today believe this level of ABSORBABLE iodine is sufficient to act as a thyroid blocker, vs. the Potassium Iodate which the body has to break down into Potassium and Iodine in order to utilize it. Cooling the reactors with sea water has caused the release of radioactive steam, which has released large quantities of radioactive trace elements into the atmosphere and environment. Some of these radioactive trace elements are known to be extremely dangerous to humans, but most of these compounds are complete unknowns as they have never been studied before, since sea water has never been used to cool reactors before. In the interest of our continued safety and the futures of our children and grandchildren, we have to assume that these radioactive trace elements are probably as dangerous as the other radioactive elements we already know about. It is thought that by supplying the body with clean non-irradiated forms of these trace elements it will limit the body’s absorption of the radioactive forms by saturating the body’s receptors for these elements, and help speed the elimination of the radioactive forms of these elements as people are exposed to these isotopes from the radioactive steam.
Full spectrum of trace minerals from sea water allows saturation of receptor sights throughout the body preventing or at least limiting the absorption of radioactive elements, including cesium, copper, zinc, selenium, strontium, calcium, sodium and others. This speeds the elimination of the radioactive version of the molecules by preferentially binding to the non-radioactive forms of the molecule. The more we can speed the elimination of the radioactive elements, the less damage is done to the body. The full spectrum trace elements are added to our reishi in the same ratios as in sea water / blood.
Notes on Research Paper Excerpts for Reishi compounds
NOTE 1: Reishi is named Ganoderma lucidum in the scientific literature.
NOTE 2: the active ingredients in Reishi are Immune Active Polysaccharides, also known as heteropolysaccharides, beta glucans, and other structures of polysaccharides. Many of these papers referenced here refer to the trials being conducted on “Glucans” or “Beta Glucans”. These are the same compounds as found in Aloha Medicinals Reishi, with one exception: the Glucans and Beta Glucans derived from medicinal mushrooms are much more bioavailable than yeast derived glucans as they have a more absorbable tertiary structure to the molecule. Most of these research papers were written in the late 80’s – early 90’s after the Chernobyl disaster. At that time the term “glucans” covered all the tertiary structures of this class of polysaccharides, as we did not then have the ability to measure the molecular shapes more accurately and assign words like “heteropolysaccharides”. However, all these research references are valid and accurate and apply to all reishi products, not just those produced by Aloha Medicinals Inc.
Thulasi G. Pillai, Cherupally Krishnan Krishnan Nair, K.K. Janardhanan; Polysaccharides isolated from Ganoderma lucidum occurring in Southern parts of India, protects radiation induced damages both in vitro and in vivo, Environmental Toxicology and Pharmacology 26 (2008) 80–85
The in vivo and in vitro radioprotective property of the polysaccharides isolated from Ganoderma lucidum were determined by survival studies, induction of micronucleus in reticulocytes of mice, strand breaks in plasmid pBR322 DNA and inhibition of lipid peroxidation (TBARS assay). Polysaccharides were administered as a single dose after whole body exposure to 10 Gy 60Co γ-radiation to Swiss albino mice. At a dose of 500µg/kg body wt, the polysaccharides were most effective in protecting animals from radiation induced loss of lethality. Administration of 500µg/kg body wt to animal exposed to 10 Gy gamma radiation resulted in more than 60% survival on the 30th day compared to the dose of 300 mg/kg/body wt administration of amifostine, a clinically used radioprotective drug. The induction of micronuclei was reduced by the administration of polysaccharides. The decrease in micronuclei induction was dose dependent. Thus following 4Gy exposure the micronuclei in polychromatic erythrocytes (MNCE) was reduced from 28.16±3.049 to 16.0243±2.074 and 6.30±2.422 by polysaccharides at doses of 250µg/kg body wt and 500 µg/kg body wt, respectively, and to 10.4±2.581 by amifostine at a dose of 300 mg/kg body wt. The results indicate the significant protective effect of Ganoderma polysaccharides against radiation induced damages. The findings thus suggest the potential use of Ganoderma polysaccharides as novel radioprotective agent.
Pillai Thulasi G. ; Salvi Veena P. ; Dharmendra Kumar Maurya ; Cherupally Krishnan Krishnan Nair ; Janardhanan K. K. ; Prevention of radiation-induced damages by aqueous extract of Ganoderma lucidum occurring in southern parts of India; Current science, 2006, vol. 91, no3, pp. 341-344
Our previous studies have demonstrated that aqueous extract of Ganoderma lucidum occurring in South India possessed significant antioxidant activity. The present study was aimed at evaluating the radioprotective properties of the aqueous extract of this mushroom. Single-cell gel electrophoresis (comet assay), protection of radiation-induced plasmid pBR322 DNA strand breaks and inhibitions of lipid peroxidation (TBARS assay) were employed to determine the level of protection offered by the extract. The results indicate that aqueous extract of G. lucidum possessed significant radioprotective activity. The findings suggest the potential use of this mushroom extract for the prevention of radiation-induced cellular damages.
Dou-Mong Hau, Wang-Chi Chen; Effects of Ganoderma lucidum on cellular immunocompetence in γ-irradiated mice; Phytotherapy Research,Volume 9, Issue 7, pages 533–535, November 1995
We have investigated the effects on mice treated with Ganoderma lucidum (GI) when the whole body was exposed to 400 rad γ-irradiation. The mice were divided into five groups. Group A was the normal control; group B, the experimental control, was treated with GI; group C was the radiation control (RT); group D was treated with RT and GI; group E was treated with GI, RT and GI. The results revealed that the relative spleen weight had increased significantly in groups B and E on day 7 and increased in all experimental groups on day 28 after irradiation. The leukocyte counts decreased obviously in groups C, D and E on day 7, and recovered in groups D and E was faster than that in group C on day 28. The blastogenic response of splenocytes to LPS, Con A and PHA in groups administered GI were higher than that in group C on days 7 and 28. Therefore, Ganoderma lucidum seemed to assist the recovery of cellular immunocompetence in γ-irradiated mice.
Huang SQ, Ning ZX; Extraction of polysaccharide from Ganoderma lucidum and its immune enhancement activity; Int J Biol Macromol. 2010 Oct 1;47(3):336-41.
In the present study, in order to maximize the yield of polysaccharides from Ganoderma lucidum, response surface methodology was employed to optimize the ultrasonic/microwave-assisted extraction (UMAE) conditions. The results indicated that the optimal extraction conditions were ultrasonic power of 50W, microwave power of 284W, extraction time of 701s and water/solid ratio of 11.6:1, respectively. Using UMAE, the yield of polysaccharides was 115.56% above that of classical hot water extraction (HWE) and increased by 27.7% as against ultrasound-assisted extraction (UAE), which confirmed the great potential application of UMAE technology in the extraction of polysaccharides. The immunological assays results demonstrated that polysaccharides of G. lucidum extracted by ultrasonic/microwave (UMP) could improve the weight of immune organ of immunocompromised mice, restore delayed-type hypersensitivity (DTH) reaction to DFNB, improve hemolysis antibody level and natural killer cell activity at high-dose. However, UMP had no noticeable effects on phagocytosis of monocyte at the tested dosage range.
Kim KC, Kim IG.; Ganoderma lucidum extract protects DNA from strand breakage caused by hydroxyl radical and UV irradiation.; Int J Mol Med. 1999 Sep;4(3):273-7.
The fruit bodies of Ganoderma lucidum have been used for the prevention and treatment of various diseases in the Orient. Its antitumor and immune enhancing properties, along with no cytotoxicity, raise the possibility that it could be effective in preventing oxidative damage and resulting disease. Using agarose gel electrophoresis, we have evaluated the potential of Ganoderma lucidum extract as a radioprotector and antioxidant defense against oxygen radical-mediated damage. Although the evidence presented here is based on in vitro using isolated DNA, the results clearly demonstrate that the hot-water extract of Ganoderma lucidum shows good radioprotective ability, as well as protection against DNA damage induced by metal-catalyzed Fenton reactions and UV irradiation. We also found that the water-soluble polysaccharide isolated from the fruit body of Ganoderma lucidum was as effective as the hot-water extract in protecting against hydroxyl radical-induced DNA strand breaks, indicating that the polysaccharide compound is associated with the protective properties. Our data suggest that Ganoderma mushroom merits investigation as a potential preventive agent in humans
Kubo N, Myojin Y, Shimamoto F, Kashimoto N, Kyo E, Kamiya K, Watanabe H., Protective effects of a water-soluble extract from cultured medium of Ganoderma lucidum (Rei-shi) mycelia and Agaricus blazei murill against X-irradiation in B6C3F1 mice: Increased small intestinal crypt survival and prolongation of average time to animal death. Int J Mol Med. 2005 Mar;15(3):401-6.
Radioprotective effects of a water-soluble extracts from cultured medium of Ganoderma lucidum (Rei-shi) mycelia (designed as MAK) and Agaricus blazei (Agaricus) against the shortening of survival time or the injury of crypt by X-irradiation were investigated in male B6C3F1 mice. MAK and Agaricus at three different doses were mixed into basal diet into biscuits at 5, 2.5 and 1.25% and administered from 1 week before irradiation. MAK (5% group) significantly prolonged animal survival as compared with basal diet group (control group) after 7 Gy of X-ray irradiation at a dose rate of 2 Gy min(-1). At doses of 8, 10 and 12 Gy X-irradiation at a dose rate of 4 Gy min(-1) MAK (5% group) significantly increased crypt survival as compared to other groups. These results suggest that MAK can act as a radioprotective agent.
Pang X, Chen Z, Gao X, Liu W, Slavin M, Yao W, Yu LL. Potential of a novel polysaccharide preparation (GLPP) from Anhui-grown Ganoderma lucidum in tumor treatment and immunostimulation.; J Food Sci. 2007 Aug;72(6):S435-42.
Growing evidence indicates the potential of developing novel polysaccharide-based adjuvant for tumor therapy from edible mushrooms, including Ganoderma lucidum. In the present study, a novel polysaccharide preparation (GLPP) was isolated from the fruiting body of G. lucidum grown in Anhui, China, and characterized for its physicochemical properties. GLPP had an average molecular weight of 6600 and a specific optical rotation of +25.6 degrees , contained 10.6% protein, and had a molar ratio of 0.9:15:1 for mannose, glucose, and galactose, respectively. GLPP was also investigated and compared with PSP (polysaccharopeptide preparation), a commercial antitumor and immunostimulating agent, for its antitumor and immunostimulation capacity, and potential in reducing the toxic effects induced by cyclophosphamide (Cy) treatment and Cobalt-60 ((60)Co) radiation in mice. GLPP at levels of 100 and 300 mg/kg body weight (BW)/d significantly inhibited the growth of inoculated S(180), Heps, and EAC tumor cells in mice. GLPP at a dose of 300 mg/kg BW/d showed stronger growth inhibition against all 3 tested tumor cells than PSP at 1 g/kg BW/d. GLPP also dose-dependently increased phagocytic index, phagocytic coefficient, and 50% hemolysin value in the EAC tumor-bearing mice, indicating its potential immunostimulating property. In addition, GLPP at 300 mg/kg BW/d was comparable to PSP at 1000 mg/kg BW/d in preventing the decrease of thymus index, spleen index, white blood cells, and bone marrow karyote numbers induced by Cy treatment and (60)Co radiation. These data demonstrated the potential utilization of GLPP as an adjuvant to conventional treatments of cancers and its use for cancer prevention.
Chung WY, Yow CM, Benzie IF. Assessment of membrane protection by traditional Chinese medicines using a flow cytometric technique: preliminary findings. Chung WY, Yow CM, Benzie IF.
In this preliminary study, we used a 'living cell' flow-cytometric approach to membrane protection by four traditional Chinese medicines (TCMs). Cells were incubated, separately, for 30 min with aqueous extracts (1.5% w/v) of lingzhi (Ganoderma lucidum), ginger (Zingiber officianale), ginseng (Panax ginseng), and green tea (Camellia sinensis). Membranes were labelled with a fluorescent probe, cells were then incubated with cumene hydroperoxide, and site-specific oxidation induced by iron/ascorbate. Oxidation of membrane lipids quenches fluorescence. Forward-scatter fluorescence was measured at timed intervals after initiation of oxidation. Results indicate that lingzhi [Ganoderma lucidum – Reishi] and ginger contain antioxidant component(s) that act within the cell membrane and slow lipid peroxidation in situ. Results demonstrate also that this living cell model is a useful biomonitoring tool to help determine molecular aspects of putative health effects of TCMs.
Jiezhong Chen, Robert Seviour; Medicinal importance of fungal b-(1/3), (1/6)-glucans; mycological research 111 (2007) 635 – 652
Non-cellulosic b-glucans are now recognized as potent immunological activators, and some are used clinically in China and Japan. These b-glucans consist of a backbone of glucose residues linked by b-(1/3)-glycosidic bonds, often with attached side-chain glucose residues joined by b-(1/6) linkages. The frequency of branching varies. The literature suggests b-glucans are effective in treating diseases like cancer, a range of microbial infections, hypercholesterolaemia, and diabetes. Their mechanisms of action involve them being recognized as non-self molecules, so the immune system is stimulated by their presence. Several receptors have been identified, which include: dectin-1, located on macrophages, which mediates b-glucan activation of phagocytosis and production of cytokines, a response co-ordinated by the toll-like receptor-2. Activated complement receptors on natural killer cells, neutrophils, and lymphocytes, may also be associated with tumour cytotoxicity. Two other receptors, scavenger and lactosylceramide, bind b-glucans and mediate a series of signal pathways leading to immunological activation. Structurally different b-glucans appear to have different affinities toward these receptors and thus generate markedly different host responses. However, the published data are not always easy to interpret as many of the earlier studies used crude b-glucan preparations with, for the most part, unknown chemical structures. Careful choice of b-glucan products is essential if their benefits are to be optimized, and a better understanding of how b-glucans bind to receptors should enable more efficient use of their biological activities.
The Biological activity of beta-glucans"; Minerva Medical; 100(3):237-245; Journal: Radiation Therapy: Jun 2009;
Beta-glucans have studied for their hypocholesterolemic effects; these mechanisms include: reducing the intestinal absorption of cholesterol and bile acids by binding to glucans; shifting the liver from cholesterol syntheses to bile acid production; and fermentation by intestinal bacteria to short-chain fatty acids, which are absorbed and inhibit hepatic cholesterol syntheses. ...beta-1,3-glucans improve the body's immune system defense against foreign invaders by enhancing the ability of macrophages, neutrophils and natural killer cells to respond to and fight a wide range of challenges such as bacteria, viruses, fungi, and parasites. ...there is renewed interest in the potential usefulness of beta-glucan as a radioprotective drug for chemotherapy, radiation therapy and nuclear emergencies, particularly because glucan can be used not only as a treatment, but also as a prophylactic [taken in advance for protection].
Kim KC, Jun HJ, Kim JS, Kim IG., Enhancement of radiation response with combined Ganoderma lucidum and Duchesnea chrysantha extracts in human leukemia HL-60 cells. Int J Mol Med. 2008 Apr;21(4):489-98
We previously demonstrated that combined treatment with extracts of the medicinal mushroom Ganoderma lucidum and the herb Duchesnea chrysantha (GDE) significantly suppresses cell growth and selectively induces apoptosis in human leukemia HL-60 cells, but not in normal cells. GDE?s mechanism of action and its activity against HL-60 cells suggest that it could be suitable for the combined-modality treatment of hematological malignancies. In the present study, we examined whether treatment with a combination of GDE and ionizing radiation enhances the therapeutic effect. We demonstrated that, when used in combination with radiation at a clinically relevant dose of 2 Gy, GDE further suppressed cell proliferation and induced apoptosis as well as micronuclei formation in HL-60 cells, leading to increased cell death. Furthermore, GDE pretreatment not only reduced radiation-induced G2/M-phase arrest, but also induced G1-phase arrest. These events are associated with the inhibition of cyclin-dependent kinase 1 (CDK1) phosphorylation and the dephosphorylation of retinoblastoma protein (pRB). Collectively, these data show that combined treatment with GDE and radiation enhances radiation-induced apoptosis and overall cell death. These findings may be clinically relevant and suggest a novel therapeutic strategy for increasing the efficacy of radiotherapy.
Jiang J, Slivova V, Sliva D. ; Ganoderma lucidum inhibits proliferation of human breast cancer cells by down-regulation of estrogen receptor and NF-kappaB signaling.; Int J Oncol. 2006 Sep;29(3):695-703.
Ganoderma lucidum, an oriental medical mushroom, has been used in Asia for the prevention and treatment of a variety of diseases, including cancer. We have previously demonstrated that G. lucidum inhibits growth and induces cell cycle arrest at G0/G1 phase through the inhibition of Akt/NF-kappaB signaling in estrogen-independent human breast cancer cells. However, the molecular mechanism(s) responsible for the inhibitory effects of G. lucidum on the proliferation of estrogen-dependent (MCF-7) and estrogen-independent (MDA-MB-231) breast cancer cells remain to be elucidated. Here, we show that G. lucidum inhibited the proliferation of breast cancer MCF-7 and MDA-MB-231 cells by the modulation of the estrogen receptor (ER) and NF-kappaB signaling. Thus, G. lucidum down-regulated the expression of ERalpha in MCF-7 cells but did not effect the expression of ERbeta in MCF-7 and MDA-MB-231 cells. In addition, G. lucidum inhibited estrogen-dependent as well as constitutive transactivation activity of ER through estrogen response element (ERE) in a reporter gene assay. G. lucidum decreased TNF-alpha-induced (MCF-7) as well as constitutive (MDA-MB-231) activity of NF-kappaB. The inhibition of ER and NF-kappaB pathways resulted in the down-regulation of expression of c-myc, finally suppressing proliferation of estrogen-dependent as well as estrogen-independent cancer cells. Collectively, these results suggest that G. lucidum inhibits proliferation of human breast cancer cells and contain biologically active compounds with specificity against estrogen receptor and NF-kappaB signaling, and implicate G. lucidum as a suitable herb for chemoprevention and chemotherapy of breast cancer
Gu YH, Takagi Y, et al; Enhancement of radioprotection and anti-tumor immunity by yeast-derived beta-glucan in mice, J Med Food. 8(2) 154-8. 2005
Intraperitoneal injection of beta-glucan was shown to greatly delay mortality in mice exposed to whole-body X-ray radiation and tumor growth in tumor-bearing mice. Since the leukocyte and lymphocyte numbers were increased by a single dose of beta-glucan, the radioprotective effect of beta-glucan is probably mediated, at least in part, by a hemopoietic action in irradiated mice. In addition, both natural killer (NK) and lymphokine-activated killer (LAK) activities were significantly increased by repeated doses of beta-glucan. Augmented immunological activity as seen in increased NK and LAK activity by beta-glucan seems to play a role in preventing secondary infections associated with irradiation, and probably contributes to the attenuated tumor growth in tumor-bearing mice through enhanced anti-tumor immunity. These results suggest that beta-glucan may be a promising adjunct treatment for cancer patients receiving radiotherapy.
Patchen M.L., MacVittie T, Jackson W; “Postirradiation glucan administration enhances the radioprotective effects of WR-2721. Radiation Research. 117:59-69. 1989
Based on murine survival studies, endogenous hemopoietic spleen colony formation (E-CFU), and recovery of bone marrow and splenic granulocyte-macrophage colony-forming cells (GM-CFC), it was demonstrated that the postirradiation administration of glucan, an immunomodulator and hemopoietic stimulant, enhances the radioprotective effects of WR-2721. LD50/30 dose reduction factors for mice treated with WR-2721 (200 mg/kg approximately 30 min before irradiation), glucan (250 mg/kg approximately 1 h after irradiation), or both agents were 1.37, 1.08, and 1.52, respectively. Enhanced survival in mice treated with both agents appeared to be due in part to glucan's ability to accelerate hemopoietic regeneration from stem cells initially protected from radiation-induced lethality by WR-2721. Following a 10-Gy radiation exposure, E-CFU numbers in mice treated with saline, WR-2721, glucan, or both WR-2721 and glucan were 0.05 +/- 0.03, 6.70 +/- 1.05, 0.95 +/- 0.24, and 33.90 +/- 2.96, respectively. Similarly, bone marrow and splenic GM-CFC numbers were greater in mice treated with both WR-2721 and glucan than in mice treated with either agent alone. These results demonstrated at least additive radioprotective effects when mice were given WR-2721 prior to irradiation and glucan following irradiation. These effects appeared to depend on the sequential cell protection mediated by WR-2721 and hemopoietic repopulation mediated by glucan.
Patchen M.L., D’Alesandro M.M., Brook I., Blakely W.F. McVittie T.J.; Glucan: Mechanisms Involved in Its ‘Radioprotective’ Effect. J Leuc Biol.; 42:95-105. 1987.
It has generally been accepted that most biologically derived agents that are radioprotective in the hemopoietic-syndrome dose range (eg, endotoxin, Bacillus Calmette Guerin, Corynebacterium parvum, etc) exert their beneficial properties by enhancing hemopoietic recovery and hence, by regenerating the host's ability to resist life-threatening opportunistic infections. However, using glucan as a hemopoietic stimulant/radioprotectant, we have demonstrated that host resistance to opportunistic infection is enhanced in these mice even prior to the detection of significant hemopoietic regeneration. This early enhanced resistance to microbial invasion in glucan-treated irradiated mice could be correlated with enhanced and/or prolonged macrophage (but not granulocyte) function. These results suggest that early after irradiation glucan may mediate its radioprotection by enhancing resistance to microbial invasion via mechanisms not necessarily predicated on hemopoietic recovery. In addition, preliminary evidence suggests that glucan can also function as an effective free-radical scavenger. Because macrophages have been shown to selectively phagocytize and sequester glucan, the possibility that these specific cells may be protected by virtue of glucan's scavenging ability is also suggested.
Pachen ML, MacVittie TJ, Comparative effects of soluble and particulate glucans on survival in irradiated mice, J Biol Response Mod 5(1):45-60. 1986.
The survival-enhancing capabilities of particulate (P) and soluble (F) glucan, a B-1,3 polyglycan biological response modifier, were assayed in 60Co irradiated mice. Although glucan-P was slightly more effective than glucan-F, both glucans significantly enhanced survival in otherwise lethally irradiated (9.0-11.0 Gy) C3H/HeN mice. Following 9.0 Gy, 60% of the glucan-P treated and 53% of the glucan-F treated mice exhibited long-term survival as opposed to 0% of the radiation control mice. The survival-enhancing effects of glucan-P and glucan-F decreased as the radiation dose increased to 11.0 Gy. At higher radiation doses (e.g., 12.0 Gy) neither glucan preparation was capable of enhancing survival. Both glucan-P and glucan-F enhanced the recovery of peripheral blood white cell numbers, platelet numbers, and hematocrit [% of volume of packed red blood cells in a blood sample] values . In addition, both agents increased endogenous pluripotent hemopoietic stem cell numbers in sublethally irradiated mice. Taken together, these results demonstrate that both glucan-P and glucan-F can significantly enhance survival in lethally irradiated mice. However, these agents appear to function specifically by enhancing hemopoietic recovery and are not effective at radiation does also known to induce gastrointestinal damage.
Toklu HZ, Sener G, Beta-glucan protects against burn-induced oxidative organ damage in rats, Int. Immunopharmacol; 6(2):156-6. 2006.
Thermal injury may lead to systemic inflammatory response, and multiple organ failure. Generation of reactive oxygen radicals and lipid peroxidation play important roles in burn-induced remote organ injury. In the present study, we investigated the putative protective effect of local or systemic beta-glucan treatment on burn-induced remote organ injury. Wistar albino rats were exposed to 90 degrees C bath for 10 s to induce thermal trauma. beta-glucan (3.75 mg/rat locally or 50 mg/kg orally) or saline was administered immediately after the trauma and were repeated twice daily in 48 h groups. Rats were decapitated either 6 or 48 h after burn injury and the skin, lung, liver, ileum and kidney tissues were taken for the measurement of malondialdehyde (MDA)--an index of lipid peroxidation--and glutathione (GSH)--a key antioxidant--levels. Neutrophil infiltration was evaluated by the measurement of tissue myeloperoxidase (MPO) activity, while the tumor necrosis factor-alpha (TNF-alpha) levels were measured in serum samples. Skin tissues were also examined microscopically. Severe skin scald injury (30% of total body surface area) caused significant decreases in GSH levels of the liver and intestinal tissues (p<0.01-<0.001), while MDA levels were significantly (p<0.01-p<0.001) increased at post-burn 6 and 48 h. Both local and systemic beta-glucan treatments significantly reversed (p<0.01-p<0.001) the elevations in MDA levels, while reduced GSH levels were reversed back to control levels (p<0.01-p<0.001); and the raised MPO levels were significantly decreased (p<0.05-p<0.001). The results indicate that both systemic and local administration of beta-glucan were effective against burn-induced oxidative tissue damage in the rat. beta-glucans, besides their immunomodulatory effects, have additional antioxidant properties. Therefore, beta-glucans merit consideration as therapeutic agents in the treatment of burn injuries.
Daniel E Cramer, Daniel J Allendorf, Jarek T Baran, Richard Hansen, Jose Marroquin, Bing Li, Janina Ratajczak, Mariusz Z Ratajczak, and Jun Yan; “Beta-glucan enhances complement-mediated hematopoietic recovery after bone marrow injury;” Blood; DOI 10.1182. Tumor Immunobiology Program and Stem Cell Biology Program, James Graham Brown Cancer Center, University of Louisville, Louisville, KY, USA. Sept 2005.
Myelotoxic injury in the bone marrow (BM) as a consequence of total body irradiation (TBI) or granulocyte colony stimulating factor (G-CSF) mobilization results in the deposition of iC3b on BM [bone marrow] stroma [cell framework]. … Taken together, these observations suggest a novel role for C, CR3, and Beta glucan in the restoration of hematopoiesis [cell formation] following injury.” NOTE: Mice were treated for 12 days with beta glucan and exposed to a sublethal dose of radiation. The beta glucan treated animals had approximately 40 percent more cell formation units in the spleen than untreated mice. When beta glucan was given orally, survival of animals receiving a lethal dose of radiation after stem cell transplantation was significantly enhanced. Forty days following radiation exposure, approximately 30 percent of mice treated with beta glucan survived compared with only 3 percent of untreated animals. NOTE: Mice were treated for 12 days with beta glucan and exposed to a sublethal dose of radiation. The beta glucan treated animals had approximately 40 percent more cell formation units in the spleen than untreated mice. When beta glucan was given orally, survival of animals receiving a lethal dose of radiation after stem cell transplantation was significantly enhanced. Forty days following radiation exposure, approximately 30 percent of mice treated with beta glucan survived compared with only 3 percent of untreated animals.
Kidd PM. The use of mushroom glucans and proteoglycans in cancer treatment. Altern Med Rev. 2000 Feb;5(1):4-27.
Immunoceuticals can be considered as substances having immunotherapeutic efficacy when taken orally. More than 50 mushroom species have yielded potential immunoceuticals that exhibit anticancer activity in vitro or in animal models and of these, six have been investigated in human cancers. All are non-toxic and very well tolerated. Lentinan and schizophyllan have little oral activity. Active Hexose Correlated Compound (AHCC) is poorly defined but has shown early clinical promise. Maitake D-Fraction has limited proof of clinical efficacy to date, but controlled research is underway. Two proteoglycans from Coriolus versicolor - PSK (Polysaccharide-K) and PSP (Polysaccharide-Peptide - have demonstrated the most promise. In Japanese trials since 1970, PSK significantly extended survival at five years or beyond in cancers of the stomach, colon-rectum, esophagus, nasopharynx, and lung (non-small cell types), and in a HLA B40-positive breast cancer subset. PSP was subjected to Phase II and Phase III trials in China. In double-blind trials, PSP significantly extended five-year survival in esophageal cancer. PSP significantly improved quality of life, provided substantial pain relief, and enhanced immune status in 70-97 percent of patients with cancers of the stomach, esophagus, lung, ovary, and cervix. PSK and PSP boosted immune cell production, ameliorated chemotherapy symptoms, and enhanced tumor infiltration by dendritic and cytotoxic T-cells. Their extremely high tolerability, proven benefits to survival and quality of life, and compatibility with chemotherapy and radiation therapy makes them well suited for cancer management regimens.
Allendorf D.J., Knudsen G., Elliott T., et al, "Oral Whole Glucan Particles Beta Glucan Treatment Accelerates Myeloid Recovery and Survival after Radiation Exposure." Center for Mind-Body Medicine Comprehensive Care Symposium, April 2003.
Oral treatment with whole glucan particles may be a useful therapeutic intervention following radiation exposure to accelerate myeloid [bone marrow] recovery and increase survival after radiation exposure.
Patchen M.L., Vaudrain T, Correira H, Martin T, Reese D, “In vitro and in vivo hematopoietic activities of Betafectin PGG-glucan.”, Exp Hematol, 26(13):1247-54. Dec 1998. Patchen M.L; Mork AC, Helmke RJ, Martinez JR, Michalek MT, Zhang GH, “Effects of particulate and soluble(1,3)-beta glucans on Ca2+ influx in NR8383 alveolar macrophages,” Immunopharmacology, 40(1):77-89. Dept of Pediatrics, U of Texas Health Science Center at San Antonio, Jul 1998.
Benefectin PGG-Glucan, a beta-(1,6) branched beta-(1,3) glucan purified from the cell walls of Saccharomyces cerevisiae, has been shown to synergize the myeloid growth factors in vitro and to enhance hematopoietic recovery in myelosuppressed mice and primates.
Patchen M.L. [V Chrm, Dept of Surg, U of Washington], et al, “Mast Cell Growth Factor(c-kit Ligand) in Combination with Granulocyte-Macrophage Colony-Stimulating Factor and Interleulin-3: in vivo Hemopoietic effects in Irradiated mice compared to in vivo effects”, Biotherapy; vol. 7. pp. 13-26. 1994.
Likewise, although both glucan and granulocyte colony-stimulating factor (G-CSF) alone enhanced survival following an 8-Gy radiation exposure, greatest survival was observed in mice treated with both agents. These studies suggest that glucan, a macrophage activator, can synergize the G-CSF to further accelerate hemopoietic [formation of blood cells] regeneration and increase survival following radiation-induced myelosuppression [bone marrow suppression].
Patchen M.L, MacVittie T.J.,”Dose-dependent responses of murine pluripotent stem cells and myeloid and erythroid progenitor cells following administration of immunomodulating agent glucan.” Immunopharmacology, 5(4):303-13, Apr 1983.
The hemopoietic effects produced by six different doses of a commercially available glucan preparation were investigated….bone marrow pluripotent stem cells (CFU-s) content increased…In the spleen, all aspects of hemopoiesis [formation of blood cells] increased after glucan administration.
Patchen M.L., McVittie T.J.; Temporal Response of Murine Pluripotent Stem Cells and Myeloid and Erythroid Progenitor Cells to Low-dose Glucan Treatment. Acta Hemat; 70:281-288. Experimental Hematology Dept, Armed Forces Radiobiology Research Insti, Bethesda, MD. 1983.
Clearly, there are numerous possible uses for an agent such as glucan, which is a potent stimulator of hemopoietic activity. Currently, we [U.S. Armed Services] are using glucan to enhance hemopoietic proliferation in conjunction with hemopoietic injury induced by radiation.
Journal: Radiation and Radiotherapy: Akramiene D, Kondrotas A, Didziapetriene J, Kevelaitis E; "Effects of beta-glucans on the immune system." Medicina (Kaunas). Dept of Physiology, Kaunas U of Medicine, Kaunas, Lithunia. 43(8):597-606; 2007.
Beta-glucans are naturally occurring polysaccharides....These substances increase host immune defense by activating complement system, enhancing macrophages and natural killer cell function. beta-Glucans also show anticarcinogenic activity. They can prevent oncogenesis due to the protective effect against potent genotoxic carcinogens. As immunostimulating agent, which acts through the activation of macrophages and NK cell cytotoxicity, beta-glucan can inhibit tumor growth...reduce tumor proliferation, prevent tumor metastasis. beta-Glucan as adjuvant to cancer chemotherapy and radiotherapy demonstrated the positive role in the restoration of hematopiesis [red blood cells] following by bone marrow injury. Immunotherapy using monoclonal antibodies is a novel strategy of cancer treatment. These [monoclonal] antibodies activate complement system and opsonize tumor cells with iC3b fragment. ...tumor cells, as well as other host cells, lack beta-glucan as a surface component and cannot trigger complement receptor 3-dependent cellular cytotoxicity and initiate tumor-killing activity. This mechanism [tumor-killing activity] could be induced in the presence of beta-glucans.
Carrow, D.J. M.D.; “Beta-1,3-glucan as a Primary Immune Activator,” Townsend Letter; June 1996.
The following list includes benefits from the use of Beta 1,3-glucan supplementation: People who have impaired immunity from any cause ...; have a high occurrence of infectious diseases; have tumors and/or those undergoing chemotherapy or radiation therapy; are over forty who are concerned about the natural aging process or might have noticed a slowing down of immune reactivity; who are geriatric patients; and other with compromised immune disorders.
Wei-Chung Liu, Shu-Chi Wang, Min-Lung Tsai, Meng-Chi Chen. Ya-Chen Wang, Ji-Hong Hong, Protection against Radiation-Induced Bone Marrow and Intestinal Injuries by Cordyceps sinensis, a Chinese Herbal Medicine.” Radiation Research 166, 900–907 (2006)
Bone marrow and intestinal damage limits the efficacy of radiotherapy for cancer and can result in death if the whole body is exposed to too high a dose, as might be the case in a nuclear accident or terrorist incident. Identification of an effective nontoxic biological radioprotector is therefore a matter of some urgency. In this study, we show that an orally administered hot-water extract from a Chinese herbal medicine, Cordyceps sinensis (CS), protects mice from bone marrow and intestinal injuries after total-body irradiation (TBI). CS increased the median time to death from 13 to 20 days after 8 Gy TBI and from 9 to 18 days after 10 Gy TBI. Although CS treated mice receiving 10 Gy TBI survived intestinal injury, most died from bone marrow failure, as shown by severe marrow hypoplasia in mice dying between 18 and 24 days. At lower TBI doses of 5.5 and 6.5 Gy, CS protected against bone marrow death, an effect that was confirmed by the finding that white blood cell counts recovered more rapidly. In vitro, CS reduced the levels of free radical species (ROS) within cells, and this is one likely mechanism for the radioprotective effects of CS, although probably not the only one.
Patchen ML, DiLuzio NR, Jacques P, MacVittie TJ. Soluble polyglycans enhance recovery from cobalt-60—induced hemopoietic injury. J Biol Response Mod. 1984 Dec;3(6):627-33.
Six soluble polyglycans (glucan-C, glucan-F, glucan-S, krestin, lentinan, and schizophyllan), two soluble polymannans (mannan-A and mannan-R), and one soluble polyfructan (levan) were assayed for their ability to enhance hemopoietic recovery in C3H/HeN mice when administered either 1 h before or 1 h after a 6.5-Gy dose of cobalt-60 radiation. Hemopoietic recovery was measured by the endogenous spleen colony assay and was compared with recovery in both radiation control mice and irradiated mice treated with glucan-P (a particulate polyglycan previously shown to enhance recovery from radiation-induced hemopoietic injury). Compared with radiation controls, when administered before irradiation, mannan-A, glucan-F, and glucan-S enhanced endogenous colony formation 4.2-5.1-fold (equivalent to glucan-P), and levan and schizophyllan approximately 2.7-fold. Lentinan, krestin, mannan-R, and glucan-C did not enhance hemopoietic recovery above radiation controls under these conditions. When polyglycan administration was delayed until after irradiation, endogenous colony formation was enhanced 3.0-3.9-fold by mannan-A, schizophyllan, glucan-S, krestin, and glucan-F (at least comparable with glucan-P) but not at all by mannan-R, levan, lentinan, or glucan-C.
Patchen ML, MacVittie TJ, Wathen LM. Effects of pre- and post-irradiation glucan treatment on pluripotent stem cells, granulocyte, macrophage and erythroid progenitor cells, and hemopoietic stromal cells. Experientia. 1984 Nov 15;40(11): 1240-4.
Glucan, a beta-1,3 polyglucose, was administered to mice either 1 h before or 1 h after a 650 rad exposure to cobalt-60 radiation. Compared to radiation controls, glucan-treated mice consistently exhibited a more rapid recovery of pluripotent stem cells and committed granulocyte, macrophage, and erythroid progenitor cells. This may partially explain the mechanism by which glucan also enhances survival in otherwise lethally irradiated mice.
Patchen ML, MacVittie TJ. Stimulated hemopoiesis and enhanced survival following glucan treatment in sublethally and lethally irradiated mice. Int J Immunopharmacol. 1985;7(6): 923-32.
Hemopoietic effects of the reticuloendothelial agent glucan were assayed in normal mice and in mice hemopoietically depleted by exposure to 60Co radiation. In normal mice, glucan administration increased the content of bone marrow and splenic transplantable pluripotent hemopoietic stem cells (CFU-s), committed granulocytemacrophage progenitor cells (GM-CFC), and pure macrophage progenitor cells (MCFC). Erythroid progenitor cells (CFU-e) were increased only in the spleen. In sublethally irradiated mice (650 rads), glucan increased the number of endogenous pluripotent hemopoietic stem cells (E-CFU) when administered either before or after irradiation. The most pronounced effects were observed when glucan was administered 1 day before, 1 h before, or 1 h after irradiation. In addition, the administration of glucan before lethal irradiation (900 rads) enhanced survival. The most significant results were seen when glucan was aministered 1 day prior to irradiation. The possibility of using agents such as glucan to enhance hemopoietic reconstitution and prevent septicemia following chemotherapy and/or radiotherapy is discussed.
Patchen ML, MacVittie TJ, Weiss JF. Combined modality radioprotection: the use of glucan and selenium with WR-2721. Int J Radiat Oncol Biol Phys. 1990 May;18(5):1069-75.
Glucan, WR-2721, and selenium, three agents with distinct radioprotective mechanisms, were evaluated in C3H/HeN mice for survival-enhancing and hemopoietic-regenerating effects when administered alone or in combinations before exposure to 60Co radiation. At LD50/30 radiation doses (radiation doses lethal for 50% of mice within 30 days postexposure), dose reduction factors of 1.21, 1.02, 1.37, 1.51, and 1.66 were obtained following glucan (75 mg/kg i.v., -20 hr), selenium (0.8 mg/kg, i.p., -20 hr), WR-2721 (200 mg/kg, i.p., -30 min), glucan + WR-2721, and glucan + selenium + WR-2721 treatments, respectively. All treatments increased numbers of hemopoietic stem cells as measured by the day 12 endogenous spleen colony-forming unit (E-CFU) assay; the most significant E-CFU effects, however, were observed following glucan + WR-2721 and glucan + selenium + WR-2721 treatments. Combined modality treatments were also more effective than single-agent treatments at accelerating bone marrow and splenic granulocyte-macrophage colony-forming cell (GM-CFC) regeneration. These results demonstrate the value of multiple-agent radioprotectants.
Patchen ML, MacVittie TJ, Solberg BD, Souza LM. Survival enhancement and hemopoietic regeneration following radiation exposure: therapeutic approach using glucan and granulocyte colony-stimulating factor. Exp Hematol. 1990 Oct;18(9):1042-8.
C3H/HeN female mice were exposed to wholebody cobalt-60 radiation and administered soluble glucan (5 mg i.v. at 1 h following exposure), recombinant human granulocyte colony-stimulating factor (G-CSF; 2.5 micrograms/day s.c., days 3-12 following exposure), or both agents. Treatments were evaluated for their ability to enhance hemopoietic regeneration, and to increase survival after radiation-induced myelosuppression. Both glucan and G-CSF enhanced hemopoietic regeneration alone; however, greater effects were observed in mice receiving both agents. For example, on day 17 following a sublethal 6.5-Gy radiation exposure, mice treated with saline, G-CSF, glucan, or both agents, respectively, exhibited 36%, 65%, 50%, and 78% of normal bone marrow cellularity, and 84%, 175%, 152%, and 212% of normal splenic cellularity. At this same time, granulocyte-macrophage colony-forming cell (GM-CFC) values in saline, G-CSF, glucan, or combination-treated mice, respectively, were 9%, 46%, 26%, and 57% of normal bone marrow values, and 57%, 937%, 364%, and 1477% of normal splenic values. Endogenous spleen colony formation was also increased in all treatment groups, with combination-treated mice exhibiting the greatest effects. Likewise, although both glucan and G-CSF alone enhanced survival following an 8-Gy radiation exposure, greatest survival was observed in mice treated with both agents. These studies suggest that glucan, a macrophage activator, can synergize with G-CSF to further accelerate hemopoietic regeneration and increase survival following radiation-induced myelosuppression.
Patchen ML, MacVittie TJ, Solberg BD, D'Alesandro MM, Brook I. Radioprotection by polysaccharides alone and in combination with aminothiols. Adv Space Res. 1992;12(2-3):233-48.
We demonstrated that glucan, a beta-1,3 polysaccharide immunomodulator, enhances survival of mice when administered before radiation exposure. Glucan's prophylactic survival-enhancing effects are mediated by several mechanisms including (1) increasing macrophage-mediated resistance to potentially lethal postirradiation opportunistic infections, (2) increasing the D(o) of hematopoietic progenitor cells, and (3) accelerating hematopoietic reconstitution. In addition, even when administered shortly after some otherwise lethal doses of radiation, glucan increases survival. Glucan's therapeutic survival-enhancing effects are also mediated through its ability to enhance macrophage function and to accelerate hematopoietic reconstitution; glucan's therapeutic potential, however, is ultimately dependent on the survival of a critical number of hematopoietic stem cells capable of responding to glucan's stimulatory effects. Preirradiation administration of the traditional aminothiol radioprotectants WR-2721 and WR-3689 has been previously demonstrated to be an extremely effective means to increase hematopoietic stem cell survival. Therapeutic glucan treatment administered in combination with preirradiation WR-2721 or WR-3689 treatment synergistically increases both hematopoietic reconstitution and survival. Such combined modality treatments offer new promise in treating acute radiation injury.
Patchen ML, Brook I, Elliott TB, Jackson WE. Adverse effects of pefloxacin in irradiated C3H/HeN mice: correction with glucan therapy. Antimicrob Agents Chemother. 1993 Sep;37(9):1882-9.
Opportunistic bacterial infections are the predominant cause of death following myelosuppressive radiation exposure. When used alone, a variety of immunomodulators and antibiotics have been reported to reduce radiation-induced death. In these studies, the combined therapeutic effects of the immunomodulator glucan and the quinolone antibiotic pefloxacin were evaluated for survival-enhancing effects in myelosuppressed C3H/HeN mice. Mice were exposed to 7.9 Gy of wholebody 60Co radiation and treated with saline, glucan (250 mg/kg of body weight intravenously, 1 h after irradiation), pefloxacin (64 mg/kg/day orally, days 3 to 24 after irradiation), or glucan plus pefloxacin. Survival 30 days after irradiation in mice receiving these respective treatments was 25, 48, 7, and 85%. Evaluation of granulocyte-macrophage progenitor cell (GM-CFC) recovery in mice receiving these treatments revealed that, compared with recovery in saline-treated mice, glucan stimulated GM-CFC recovery, pefloxacin suppressed GM-CFC recovery, and glucan administered in combination with pefloxacin could override pefloxacin's hemopoietic suppressive effect.
Hofer M, Pospisil M. Glucan as stimulator of hematopoiesis in normal and gamma-irradiated mice. A survey of the authors' results. Int J Immunopharmacol. 1997 Sep- Oct;19(9-10):607-9.
Glucan, a beta-1,3-linked polyglucose derived from the yeast Saccharomyces cerevisiae, is a broad spectrum enhancer of host defense mechanisms stimulating humoral and cell-mediated immunity. On the basis of these features, glucan has been tested by the authors' research group in experiments on gamma-irradiated mice. Two glucan forms, particulate and soluble, have been studied. Attention has been focused on various application regimens in relation to the time of irradiation (pre- or postirradiation application), the possibilities of using glucan in various radiation regimens (single or repeated irradiation), combined pharmacological therapy (joint administration of glucan with cystamine or inhibitors of prostaglandin synthesis), and on the negative side effects of therapy with glucan. Some studies included also experiments on unirradiated mice. The results have demonstrated the ability of glucan to influence positively the course of the acute radiation disease. Stimulation of hematopoiesis has been found to be the most important mechanism of glucan's radioprotective effects. In this communication, the results of 11 full-length articles are summarized and discussed.
Chertkov KS, Davydova SA, Nesterova TA, Zviagintseva TN, Eliakova LA.Efficiency of polysaccharide translam for early treatment of acute radiation illness. Radiats Biol Radioecol. 1999 Sep- Oct;39(5):572-7. Russian.
Antiradiation therapeutic efficiency of translam (1-->3; 1-->6-beta-D-glucan) produced by enzymatic synthesis out of laminarin, polysaccharide of Laminaria cychorioides, has been studied in four animal species (mice, guinea-pigs, dogs, monkeys). A stable curative effect has been observed following its administration within first 24 h after radiation exposure at doses that cause acute radiation sickness (about LD90). The preparation is nontoxic and has a broad therapeutic range which permits its practical application.
Kuznetsova TA, Krylova NV, Besednova NN, Vasil'eva VN, Zviagintseva TN, Krashevskii SV, Eliakova LA. The effect of translam on the natural resistance indices of the irradiated organism. Radiats Biol Radioecol. 1994 Mar- Apr;34(2):236-9. Russian.
It has been studied the influence of translam-beta-1,3; 1,6-glucan, extracted from seaweed Laminaria, on the isolation of E. coli from spleen and on the functional activity of peritoneal macrophages of sub-lethal irradiated and infected mice. It has been shown the reduction of the number of microbes, isolated from spleen and stimulation of ingestive and digestive activity of macrophages following the introduction of translam in mice. This results show about the increase of natural resistance of irradiated organism under translam action and characterize this glucan as effective stimulator of immunity.
Zaporozhets TS, Besednova NN, Eliakova LA, Zviagintseva TN, Krashevskii SV. The effect of translam on the immune response of irradiated mice. Radiats Biol Radioecol. 1995 Mar- Apr;35(2):260-3. Russian.
Experimental facts about influence of new beta-1-3;1-6-glucan, extracted from seaweed Laminaria, on immune response of mice are summarized. The ability of translam to increase the number and functional activity of immunocompetent cells taking part in humoral immune response formation. The possibility of translam using for treatment and prophylaxis of radiation affections is discussed.
Pospisil M, Hofer M, Pipalova I, Viklicka S, Netikova J, Sandula J. Enhancement of hematopoietic recovery in gamma-irradiated mice by the joint use of diclofenac, an inhibitor of prostaglandin production, and glucan, a macrophage activator. Exp Hematol. 1992 Aug;20(7):891-5.
The effects of diclofenac (inhibitor of prostaglandin production) and carboxymethylglucan (immunomodulator and an agent stimulating hematopoiesis), when given to mice 1 day before gamma-irradiation, were studied. Both of the agents were administered either alone or in combination. The investigations included the assessment of post-irradiation hematopoietic recovery in terms of bone marrow and spleen cellularity and endogenous spleen colony formation, as well as the determination of the survival of lethally irradiated mice. The results demonstrated at least additive radioprotective effects when mice were given diclofenac and carboxymethylglucan in combination. Experimental evidence provided by the increased 125iodo-deoxyuridine incorporation into the spleen and elevated hydroxyurea kill of endogenous spleen colony-forming units indicated that the beneficial action of the combined treatment could be a consequence of increased cell proliferation in the hematopoietic tissue. It is likely that the inhibition of prostaglandin production (diclofenac action) and the concomitant increased release of growth factors (glucan action) shift the regulatory balance towards the predominance of positive hematopoietic control.
Nakano T, Oka K, Sugita T, Tsunemoto H. Antitumor activity of Langerhans cells in radiation therapy for cervical cancer and its modulation with SPG administration. In Vivo. 1993 May-Jun;7(3):257-63.
Correlations between infiltration of Langerhans cells (ILC) in tumor tissues and radiation curability were investigated in 449 patients with cervical cancer treated with radiation alone, including 390 squamous cell carcinomas and 59 adenocarcinomas. No significant difference in prognosis was noted in stage I, II, and IV squamous cell carcinomas between positive and negative ILC. However, in the patients with stage III squamous cell carcinoma, a significantly better survival was observed for patients with ILC than for those without, 10 year survival rates being 78% vs. 54%, P < 0.01. In adenocarcinoma, the patients with ILC also showed significantly better survival than those without ILC, the 10 years survival rates being 45% vs. 25%, P < 0.025. An analysis of failure patterns following radiation treatment demonstrated that the favorable prognosis in patients with ILC in squamous cell carcinoma was due to improvement of local control rates and somewhat lower metastatic rates, whereas in adenocarcinoma it was only due to better local control rate. The ILC was significantly associated with T-cell infiltration in tumor tissues. The immunological stimulation with Sizofiran in 20 patients led to an augmentation of ILC in tumor tissues. The present study suggests that the ILC in cancer tissues improves local response to radiation treatment partly by T-cell mediated anti-tumor activity.
Arika T, Amemiya K, Nomoto K. Combination therapy of radiation and Sizofiran (SPG) on the tumor growth and metastasis on squamous-cell carcinoma NR-S1 in syngeneic C3H/He mice. Biotherapy. 1992;4(2):165-70.
The efficacy of Sizofiran(SPG), a highly purified beta-1,3-D-glucan from the culture broth of basidiomycetes Schizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of C3H/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected IM at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C-treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy.
Sekiguchi I, Suzuki M, Izumi A, Aida I, Tamada T. The study on the immunological effect of sizofilan combined with radiotherapy in patients with uterine cervical cancer. Nippon Gan Chiryo Gakkai Shi. 1990 Nov 20;25(11):2659-64. Japanese.
To investigate the immunological effect of Sizofilan (SPG) combined with radiotherapy, we evaluated the immunological parameters in 22 patients with uterine cervical cancers. Twelve cases were treated with SPG combined with radiotherapy (SPG group), and the other ten cases, with radiotherapy only (control group). As a result, 1) During radiotherapy, the numbers of lymphocyte and CD2 positive cell decreased in SPG and control groups. After radiotherapy, however, its numbers in SPG group became significantly higher than in control group (p less than 0.05). The number of CD3 positive cell also presented a tendency to increase after radiotherapy in SPG group. As for CD20 positive cell, its numbers were kept unchanged after radiotherapy in both two groups, and no significant difference was observed between them. 2) NK cell activity decreased during radiotherapy in both two groups. After radiotherapy, its activity in SPG group recovered to its pre-value and became significantly higher than that in control group (p less than 0.05). 3) SPG did not any prominent effect on CD4/CD8 ratio. 4) The adverse effect of SPG to liver or kidney function were not observed in our patients. The SCC level in SPG group decreased rapidly by radiotherapy as well as that in control group, and no significant difference was observed in SCC levels between them. So it was suggested that SPG did not suppress the cytocidal effect of radiation to cancer cells. Based on these findings, it was concluded that SPG prompted the recovery of not only lymphocyte, especially T cell, but also NK cell activity. These immunological findings presented a usefulness of clinical application of SPG to radiotherapy in patients with uterine cervical cancers.
Maisin JR, Albert C, Henry A. Reduction of short-term radiation lethality by biological response modifiers given alone or in association with other chemical protectors. Radiat Res. 1993 Sep;135(3):332-7.
The advantages gained by a combined treatment of different chemical protectors on short-term lethality of X-irradiated adult male mice have been studied. The following compounds were given alone or in a mixture of two or three compounds: 16,16- dimethyl PGE2 (PGE2), cysteine (Cys), glucan, glutathione (GSH), 5- hydroxytryptamine (5-HT), mercaptoproprionylglycine (MPG), or WR-2721. The survival of mice treated before X irradiation with the optimal dose of each radioprotector given separately shows that WR-2721 and 5-HT yield the best protection with dose reduction factors (DRFs) of 2.2 and 1.7, respectively. Cysteine, glucan, PGE2, MPG, and GSH, with DRFs of 1.4, 1.4, 1.2, 1.1, and 1.1, respectively are less efficient radioprotectors. When PGE2 was combined with a low dose of WR- 2721 (200 mg/kg), the protection increased in a synergistic way. The increase in protection offered by a combination of PGE2 with Cys, glucan, GSH, or 5-HT is less marked and the effect obtained is only additive. A synergistic action is also obtained with a combination of WR-2721 (200 mg/kg) and 5-HT (8 mg/kg) (DRF 2.7).
Hofer M, Pospisil M, Viklicka S, Vacek A, Pipalova I, Bartonickova A. Hematopoietic recovery in repeatedly irradiated mice can be enhanced by a repeatedly administered combination of diclofenac and glucan. J Leukoc Biol. 1993 Feb;53(2):185-9.
A combination of diclofenac and glucan administered repeatedly in a protective regimen in the course of repeated gamma irradiation of mice (6 x 2 Gy during 3 weeks) enhanced granulopoiesis and other indices of hematopoietic recovery investigated from 3 to 7 days after the last radiation exposure. Repeated administration of diclofenac or glucan alone or treatment of the mice with the diclofenac-glucan combination given once before the first or the last radiation exposure did not induce such effects. The protective effect of the repeatedly administered combination of the drugs was realized despite the fact that the response of the serum colony-stimulating activity to the repeated combined drug administration was decreased at the end of the treatment regimen compared to that of mice given this drug combination only once. The combined treatment is supposed to act via increased proliferation of the hematopoietic stem or progenitor cells. Additivity or even synergism of the hematostimulatory action of glucan and of the strengthening of positive control of cell proliferation achieved by removing negatively acting prostaglandins (diclofenac action) may account for the radioprotective effects observed.
Chorvatovicova D. Suppressing effects of glucan on micronuclei induced by Co60 in mice. Strahlenther Onkol. 1991 Oct;167(10):612-4.
The effects of glucan on the frequency of micronuclei in polychromatic erythrocytes of A/Ph mouse bone marrow induced by Co60 irradiation were examined. Suppressing effect of three glucan derivatives was statistically significant (P less than 0.01) by intravenous application of glucan one hour after irradiation. The most expressive effect was obvious by K3 substituent (DS 0.89). Intraperitoneal application of glucan has to be done earlier than one hour after irradiation. The suppressive effects of glucans can be explained by their ability to trap OH radicals and so decrease the clastogenic effect of irradiation. The results may be useful for therapeutic application of glucan with radiation therapy.
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