Monthly Archives: September 2010

Immunotherapy, Medical Studies, PSP

Immunomodulatory effects of polysaccharopeptide (PSP) in human PBMC through regulation of TRAF6/TLR immunosignal-transduction pathways.

Li W, Liu M, Lai S, Xu C, Lu F, Xiao X, Bao Y.

Department of Clinical Laboratory, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Context: Polysaccharopeptide (PSP) was extracted from Coriolus versicolor, and has been proved to be a valuable adjuvant for the combination with chemotherapy or radiotherapy in the treatment of various cancers. Objective: To understand the mechanism of PSP on immunomodulation, we examined gene expression and cytokine secretion associated with immunosignal-transduction signaling in human peripheral blood mononuclear cells (PBMCs). Methods: cDNA microarray and cytokine antibody array were used to identify differential gene expression profiles and cytokines secretion of PBMCs in the presence or absence of PSP for 24 h. The expression of the key genes and proteins related to Toll-like receptor (TLR) signaling and its downstream pathway was determined by RT-PCR or Western blot. Results: Compared with the control group, PSP up-regulated 22 genes expression (such as IFN-gamma, CXCL10, TLR4, TLR5) in 117 genes associated with TLR signaling. Twenty-three of genes (e.g., TLR9, TLR10, SARM1, TOLLIP) related with TLR signaling pathway were down-regulated in PBMCs under PSP treatments. Five of cytokines (GCSF, GM-CSF, IL-1alpha, IL-6, IFN-gamma) were up-regulated more than 1.3 times by PSP. The mRNA levels of TRAM, TRIF, and TRAF6, which are the key molecules of TLR signaling pathway, were markedly increased (P < 0.05). Moreover, the protein level of TRAF6 was also markedly increased (P < 0.01). Conclusions: PSP-regulated gene expression and cytokine secretion related to TLR signaling pathway in human PBMCs. Especially, TRAM-TRIF-TRAF6 subsignaling pathway of TLR may be one of the key associated signaling pathways in the immunomodulation of PSP.

PMID: 20131955 [PubMed – as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20131955

Medical Studies

Effect of nitrogen sources and vitamins on ligninolytic enzyme production by some white-rot fungi. Dye decolorization by selected culture filtrates

1 Comment

Levin L, Melignani E, Ramos AM.

Lab. de Micología Experimental, Dpto. de Biodiversidad y Biología Experimental, Fac. Cs. Exactas y Naturales, PROPLAME – PRHIDEB – CONICET, Universidad de Buenos Aires, C1428EHA Ciudad Universitaria, CABA, Argentina. lale@bg.fcen.uba.ar

Abstract

The effect of amino acids, complex nitrogen sources and vitamin addition on Trametes trogii, Trametes villosa and Coriolus versicolor var. antarcticus ligninolytic enzyme production, was evaluated. Dye decolorization by their culture filtrates was compared. Glutamic acid followed by peptone, were the best N sources for laccase and manganese peroxidase production. The three fungi produced two laccase isoenzymes (molecular weights from 38 up to 150 kDa); their pattern of production was not affected by medium composition. Although the response was not uniform, vitamin addition sometimes stimulated ligninolytic enzyme production, but never inhibited it. Thiamine induced manganese peroxidase production. T. trogii grown in glutamic acid produced culture filtrates with the highest laccase (188.3 U/ml) and manganese peroxidase activities (4.5 U/ml), rendering the best results in decolorization. These crude filtrates were able to decolorize in half hour (at pH 4.5, 30 degrees C): 13%, 23%, 40%, 46%, 82%, 94% and 95% of Gentian Violet, Xylidine, Congo Red, Malachite Green, Remazol Brilliant Blue R, Indigo Carmine and Anthraquinone Blue, respectively.

http://www.ncbi.nlm.nih.gov/pubmed/20153961

Medical Studies

Investigation of growth responses in saprophytic fungi to charred biomass.

Ascough PL, Sturrock CJ, Bird MI.

SUERC, Scottish Enterprise Technology Park, East Kilbride, UK. p.ascough@suerc.gla.ac.uk

Abstract

We present the results of a study testing the response of two saprophytic white-rot fungi species, Pleurotus pulmonarius and Coriolus versicolor, to charred biomass (charcoal) as a growth substrate. We used a combination of optical microscopy, scanning electron microscopy, elemental abundance measurements, and isotope ratio mass spectrometry ((13)C and (15)N) to investigate fungal colonisation of control and incubated samples of Scots Pine (Pinus sylvestris) wood, and charcoal from the same species produced at 300 degrees C and 400 degrees C. Both species of fungi colonise the surface and interior of wood and charcoals over time periods of less than 70 days; however, distinctly different growth forms are evident between the exterior and interior of the charcoal substrate, with hyphal penetration concentrated along lines of structural weakness. Although the fungi were able to degrade and metabolise the pine wood, charcoal does not form a readily available source of fungal nutrients at least for these species under the conditions used in this study.

PMID: 20229385 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/pubmed/20229385

Cancer, Leukemia, Medical Studies, PSP

Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells.

Wan JM, Sit WH, Yang X, Jiang P, Wong LL.

Agricultural, Food and Nutritional Sciences Division, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, Hong Kong SAR, China. jmfwan@hkusua.hku.hk.

Abstract

ABSTRACT:

BACKGROUND: Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).

METHODS: We used bivariate bromodeoxyuridine/propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.

RESULTS: PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.

CONCLUSION: The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.

PMID: 20423495 [PubMed – in process]PMCID: PMC2874562

http://www.ncbi.nlm.nih.gov/pubmed/20423495

Cancer, Immunotherapy, Interleukin, Medical Studies

Antimetastatic and immunomodulating effect of water extracts from various mushrooms.

Han SS, Cho CK, Lee YW, Yoo HS.

East-West Cancer Center, College of Oriental Medicine, Daejeon University, Daejeon, Korea.

Abstract

This experiment was conducted to evaluate inhibitory effects against lung metastasis and promotion of splenocytes by water extracts from various mushrooms including Armillaria mellea, Grifola frondosa, Garnoderma frondosa, Codyceps militaris, Hericium erinaceus, Coriolus versicolor, Agaricus Blazei with Lycium Chinense Miller (known as M8). Analysis of carbohydrate using HPTLC showed that beta-glucan and pachyman were some of the major components of M8. Oral administration of M8 resulted in a dose-dependent tendency to inhibit lung metastasis after intravenous injection of colon26-L5 cells. Treatment with M8 resulted in a significant increase of T cell and B cell mitogenic stimuli. The population of CD3, CD19, CD4, and CD8 positive cells increased in a dose dependent manner of M8 administration. However, no significant results were obtained from the population of Mac-1 and NK1.1 positive cells. Oral administration of M8 resulted in the increased production of IFN-gamma and IL-4 by splenocytes stimulated with Con A compared with untreated controls. These results show that M8 has antitumor activities which may be useful as an antimetastatic agent.

PMID: 20633495 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/pubmed/20663037

Autoimmune Disease, Lymphocytes, Medical Studies, PSP

Regulatory properties of polysaccharopeptide derived from Coriolus versicolor and its combined effect with ciclosporin on the homeostasis of human lymphocytes.

Lee CL, Jiang P, Sit WH, Yang X, Wan JM.

School of Biological Sciences, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam Road, Hong Kong SAR.

Abstract

OBJECTIVES: Lymphocyte homoeostasis is essential in inflammatory and autoimmune diseases. In search of natural fungal metabolites with effects on lymphocyte homoeostasis, we recently reported that polysaccharopeptide (PSP) from Coriolus versicolor exhibited ciclosporin-like activity in controlling aberrant lymphocyte activation. This object of this study was to investigate its effect on lymphocyte homoeostasis. This was done by investigating the mechanistic actions of PSP in relation to ciclosporin by performing cell cycle and cell death analysis of human lymphocytes in vitro.

METHODS: We investigated the effect of PSP in the presence and absence of ciclosporin on cell proliferation, cell cycle, cell death, immunophenotype and cell cycle regulatory proteins in human lymphocytes.

KEY FINDINGS: The data showed that PSP exhibited homoeostatic activity by promoting and inhibiting the proliferation of resting and phytohaemagglutinin (PHA)-stimulated lymphocytes, respectively. PHA-stimulated lymphocytes exhibited G0/G1 cell cycle arrest that was accompanied by a reduction of cyclin E expression with PSP treatment. Both PSP and ciclosporin blocked the reduction of the CD4/CD8 ratio in stimulated lymphocytes. PSP did not induce cell death in human lymphocytes, but the suppression of the Fasreceptor suggested a protective role of PSP against extrinsic cell death signals. These homoeostatic effects were more potent with combined PSP and ciclosporin treatment than with either fungal metabolite alone.

CONCLUSIONS: Collectively, the results reveal certain novel effects of PSP in lymphocyte homoeostasis and suggest potential as a specific immunomodulatory adjuvant for clinical applications in the treatment of autoimmune diseases.

PMID: 20663037 [PubMed – in process]

http://www.ncbi.nlm.nih.gov/pubmed/20663037

Cancer, Clinical Trials, Gastric Cancer, Immunotherapy, Medical Studies, PSK

Alternating immunochemotherapy of advanced gastric carcinoma: a randomized comparison of carbazilquinone and PSK to carbazilquinone in patients with curative gastric resection.

A total of 103 patients with advanced gastric carcinoma were randomized after curative surgery to receive an alternate administration of carbazilquinone (CQ) and PSK (Krestin) or carbazilquinone alone. Each course of therapies started 1 week after the surgical operation and therapy schedules consisted of 9 courses. In each course of 6 weeks, CQ (2 mg/m2/week) was administered on day 0, 8, and 15. In combined immunochemotherapy group, PSK was given orally in 3-divided doses of 2 g/m2/day from the day of the third CQ administration for consecutive 4 weeks. Estimated survival rate and cumulative survival curve were compared utilizing the data up to 7 years after the operation. There was no overall significant difference in survival rates between the CQ plus PSK group and the CQ alone group, but a group of patients whose disease was classified as S1 + S2(N1-2) survived significantly longer when treated with the combination of CQ and PSK. Neither in more advanced cases (greater than S3 or greater than N3) nor in cancers of early stages, the addition of PSK provided an additive effect. The favorable result obtained in one subgroup treated with PSK, suggests that the use of this agent in treating gastric cancers should be carefully evaluated in terms of serosal infiltration and nodal metastasis.

Clinical Trials, Colorectal Cancer, Immunotherapy, Medical Studies, PSK

Adjuvant therapy with protein-bound polysaccharide K and tegafur uracil in patients with stage II or III colorectal cancer: randomized, controlled trial.

PURPOSE: Intravenous fluorouracil and leucovorin for six to eight months is currently a standard adjuvant treatment for Stage III colon cancer; however, this regimen is complex, inconvenient, and has a high intolerability. Adjuvant chemotherapies are claimed for objective response rates with an acceptable safety profile and complexity. We investigated the benefits of oral protein-bound polysaccharide K added to oral tegafur/uracil on curatively resected Stage II or III colorectal cancer. METHODS: We prospectively randomized 207 patients to treatments of either oral 3.0 g protein-bound polysaccharide K plus 300 mg tegafur/uracil or 300 mg tegafur/uracil alone for two years following 12 mg/m2 and 8 mg/m2 mitomycin treatment on postoperative Days 1 and 2, respectively. The primary end points were disease-free and overall survival, and recurrence rates. RESULTS: Three (1.4 percent) patients were declared ineligible, and three patients did not start treatment. In total, 201 patients were analyzed. The three-year, disease-free survival rate was 80.6 percent (standard error = 3.4 percent) in the protein-bound polysaccharide K group (P = 0.02) compared with 68.7 percent (SE = 5.7 percent) in the control group after a median follow-up of 3.7 years. The estimated relative risk of recurrence in the control group was 1.87 (95 percent confidence interval, 1.10-3.20) at three years. The three-year, overall survival rate was 87.3 percent (standard error = 2.9 percent) in the protein-bound polysaccharide K group and 80.6 percent (standard error = 4.8 percent) in the control group (P = 0.24). The three-year, overall survival rate in 80 pathological TNM Stage III patients was 83.0 percent (standard error = 5.2 percent) in the protein-bound polysaccharide K group and 59.3 percent (standard error = 9.5 percent) in the control group (P = 0.02). Protein-bound polysaccharide K prevented distant metastases (P = 0.05), particularly lung metastases (P = 0.01). The incidence of adverse effects was minimal, and compliance was good. CONCLUSION: Adjuvant therapy using a combination of oral protein-bound polysaccharide K and tegafur/uracil is highly effective in preventing the recurrence of colorectal cancer in Stage II or III patients, and increases overall survival in pathological TNM Stage III. These results will be a sufficient proof to conduct a larger study to compare tegafur/uracil/protein-bound polysaccharide K with 5-fluorouracil/leucovorin.

Immunotherapy, News, PSK, PSP

Introducing inForce Immune Builder

Irvine, California (September 7, 2010) inLife, LLC, distributors of science-based Health & Wellness products, today introduced inForce Immune Builder, a new product that clinical research shows helps stimulate the body’s immune system. inForce’s main ingredient, the Coriolus versicolor mushroom mycelia extract, is one of the most widely studied supplements for its immune building properties and is now available to the public and the direct-selling industry. Worldwide, there have been over 400 animal and human studies on Coriolus versicolor, with over a dozen placebo-based human trials conducted in the west.

inLife Immune Builder with PSP and PSK
inLife offers Coriolus versicolor as a Daily Dietary Supplement in vegan capsule form to help maintain and stimulate the body’s immune system. Coriolus versicolor, PSK and PSP are among the most widely studied supplements for their immune building properties. One would be hard pressed to find another immune boosting product that has had more research completed or positive comments associated with it. The amount of worldwide comments and studies is compelling. inForce Immune Builder is a proprietary blend of both Polysaccharide-K (PSK) and Polysaccharide Peptide (PSP). Both offer much-needed immune building assistance and they can be taken on a daily basis. The products are bottled in the United States in an FDA-registered bottling facility that is cGMP compliant (Current Good Manufacturing Practices).

Hospital and Research Institutes Report on Coriolus Versicolor
In the United States, top-ranked hospital and research institutes have reported that “Coriolus versicolor, PSK and PSP help boost the body’s immune system with limited side effects and safety of daily oral doses for extended periods of time.” In addition, Coriolus versicolor and its potential positive effects has been studied very closely by M.D. Anderson, University of Texas, Loma Linda University, Beth Israel Deaconess Medical Center (a teaching hospital of Harvard Medical School) , The University of San Diego, Sloan-Kettering Center (New York), and Bastyr University (Kenmore, Washington), just to name a few.

About inLife, LLC
Founded in 2007, inLife has been very successful in bringing to the market products that have efficacies that are soundly based on scientific research. inLife products are now available in the U.S. as well as the U.K, Canada and Spain. For more information on inForce Immune Builder and the company, please review www.myinlife.com. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

# # #

Founded in 2007, inLife has been very successful in bringing to the market products that have efficacies that are soundly based on scientific research. inLife products are now available in the U.S. as well as the U.K, Canada and Spain.

Click here to download this press release.

Autoimmune Disease, Chronic Fatigue Syndrome, Clinical Trials, Fibromyalgia, Medical Studies, Preventative

Mushroom immunutrition in Chronic Fatigue Immune Dysfunction Syndrome

In the recently published edition of the Journal of Integrated Medicine (Online version), Dr. Jean Monro of the Breakspear Hospital outlines the impact of Coriolus versicolor supplementation as immunonutrition in thirty-six (36) Chronic Fatigue Immune Dysfunction Syndrome (CFIDS) patients over a six week period.

The 36 patients were selected on the basis of international criteria for the diagnosis of CFIDS. Ages ranged from 17 years to 83 years and there was a female-to-male ratio of 2:1. In addition, the patients had a combination of high antibody levels to Epstein Barr virus (EBV) and/or Herpes Simplex 6 virus (HHV6) and/or Cytomegalovirus. (CMV).

Patients were given Coriolus versicolor (non-extracted) 6 tablets daily for 15 days (3 g/day), followed by 3 tablets daily for 45 days (1.5 g/day). Immune parameters were measured before and after the sixty (60) day supplementation period.

Results were noted in two areas:

1) Natural Killer Cells–before treatment the average NK cell level was average=129.64/mm3. After treatment this had increased to 175/mm3, an increase of 35%.

2) T cells (CD3 CD26)–there was increased activation in 66% of patients and T cell depression in 22% of patients. T cell level was unchanged in 11% of the patients.

Conclusion

Supplementation with non-extracted Coriolus versicolor showed improvements in both immune parameters and viral levels in the majority of the thirty-six (36) CFIDS patients, indicating that Coriolus versicolor supplementation has the potential to play a significant role in the treatment of CFIDS.