Category Archives: Diseases

Morphological study of cytotoxicity produced by PSK-induced polymorphonuclear leukocytes (PMNs) and Nocardia rubra cell wall skeleton.

Kata H, Inoue M, Mukai S, Kawahito Y, Yoshida T, Asai K, Kimura S, Hashiramoto A, Yamamura Y, Sano H, Sugino S, Kondo M.

First Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.

Abstract

The morphologic changes in PMNs induced by an i.p. injection of PSK, a polysaccharide from the mycelia of Coriolus versicolor, and tumor cells undergoing cell death, were evaluated by immunohistochemical staining and electron microscopy. Male C3H/He mice, 8-10 -weeks old, received an i.p. injection of 125 mg/kg of PSK. Their PMNs were obtained 6 h after the PSK injection by peritoneal lavage. N-CWS (Nocardia rubra cell wall skeleton) was added at the start of the chromium release assay using the MM46 mammary carcinoma cell line, which is syngeneic to C3H/He mice, as target cells. During the cytotoxic assay, the cells were fixed at various time points. The MM46 cells expressed ICAM-1 while the PMNs expressed both ICAM-1 and LFA-1 as determined by immunohistochemical staining and immunoelectron microscopy using anti-ICAM-1 and anti-LFA-1 antibodies. PMNs with ruffle-like microvilli adhered to the MM46 tumor cells 30 min after the addition of N-CWS. Immunoelectron microscopic findings suggested that the adhesion molecules were LFA-1 on the PMNs and ICAM-1 on the MM46 tumor cells, but cell fusion between the PMNs and tumor cells was not observed. The MM46 tumor cells gradually lost their microvilli, which showed cell damage, and died 6-7 h after the addition of the N-CWS. This time course of tumor cell death is compatible with the results of the cytotoxic assay. Pretreatment of PMNs by anti-LFA-1 antibody suppressed 1% lysis of MM46 tumor cells from 90% to 10% (p < 0.01). These data suggest that adhesion molecule on the surface of PMNs such as LFA-1 might play an important role on signal transduction of these PMNs cytotoxic function in this experimental system.

PMID: 9012542 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9012542

Dose intensity of uracil and tegafur in postoperative chemotherapy for patients with poorly differentiated gastric cancer.

Sugimachi K, Maehara Y, Ogawa M, Kakegawa T, Tomita M.

Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.

Abstract

A retrospective analysis of postoperative chemotherapy had shown the continuous administration of UFT, an oral preparation of 1-(2-tetrahydrofuryl)-5-fluorouracil (tegafur) and uracil at a molar ratio of 1:4, to be effective for poorly differentiated gastric cancer. We therefore sought to determine prospectively the effective dose of postoperative chemotherapy with UFT for patients with poorly differentiated gastric cancer following a curative resection. We determined the effect of the combined intravenous administration of mitomycin C (MMC) and oral treatment with protein-bound polysaccharide Kreha (PSK), extracted from the basidiomycete Coriolus versicolor, and UFT at a dose of either 8 mg/kg or 12 mg/kg daily for 1 year. A total of 224 patients with poorly differentiated stage II-IV gastric cancer were entered into this study after undergoing a curative resection. No differences were observed between the two treatment groups in terms of prognostic factors, the toxicity rate or the doses of the drugs prescribed, other than UFT. The higher dose of UFT in maintenance therapy led to a decrease in the recurrence rate (P < 0.05), and increases in disease-free survival and cause-specific survival (P < 0.05). UFT at 12 mg/kg in postoperative chemotherapy was thus found- to improve the postoperative results with no increase in toxicity for poorly differentiated gastric cancer, and is also cost-effective for outpatients.

PMID: 9219507 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9219507

Effects of OK-432 (picibanil) on the estrogen receptors of MCF-7 cells and potentiation of antiproliferative effects of tamoxifen in combination with OK-432.

Aoyagi H, Iino Y, Takeo T, Horii Y, Morishita Y, Horiuchi R.

Second Department of Surgery, Gunma University School of Medicine, Maebashi, Japan.

Abstract

OK-432 (picibanil), a streptococcal preparation, has a strong biological response modifier (BRM) function and is expected to produce clinical improvement and prolongation of survival in treated cancer patients in Japan. We were interested in whether OK-432 augments estrogen receptor (ER) levels in breast cancer. To investigate the effect of the BRMs on cellular growth and the characteristics of ER and progesterone receptors (PgR) in the human breast cancer cell line MCF-7, we used OK-432, Krestin (PSK), a protein-bound polysaccharide extracted from Coriolus versicolor, and lentinan, a fungal branched (1…3)-beta-D-glycan. OK432 and PSK dose dependently inhibited DNA synthesis of MCF-7 cells, and the 50% inhibitory concentrations of OK-432 and PSK were 1.2 KE (klinische Einheit, clinical unit)/ml and 200 micrograms/ml, respectively. Lentinan showed no direct anticancer effect in vitro. We found that OK-432 induced a 2-fold increase in ER levels in MCF-7 cells at 0.005 KE/ml, but not in PgR. Lentinan and low-dose PSK did not change ER or PgR levels, but high-dose PSK decreased ER and PgR. We also studied the combined effect of OK-432 and antiestrogens, tamoxifen (TAM) and DP-TAT-59. The combined treatment with OK-432 and TAM showed an additive inhibitory effect on MCF-7 cells. These results suggest that OK-432 may augment the therapeutic effect of TAM in breast cancer.

PMID: 9260604 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/9260604

The use of mushroom glucans and proteoglycans in cancer treatment.

Kidd PM.

Abstract

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.

PMID: 10696116 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/10696116

Immunomodulation and anti-cancer activity of polysaccharide-protein complexes.

Ooi VE, Liu F.

Department of Biology, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.

Abstract

In the last three decades, numerous polysaccharides and polysaccharide-protein complexes have been isolated from mushrooms and used as a source of therapeutic agents. The most promising biopharmacological activities of these biopolymers are their immunomodulation and anti-cancer effects. They are mainly present as glucans with different types of glycosidic linkages such as (1–>3), (1–>6)-beta-glucans and (1–>3)-alpha-glucans, and as true herteroglycans, while others mostly bind to protein residues as polysaccharide-protein complexes. Three antitumor mushroom polysaccharides, i.e. lentinan, schizophyllan and protein-bound polysaccharide (PSK, Krestin), isolated respectively, from Lentinus edodes, Schizophyllum commune and Coriolus versicolor, have become large market items in Japan. Lentinan and schizophyllan are pure beta-glucans, whereas PSK is a protein-bound beta-glucan. A polysaccharide peptide (PSP), isolated from a strain of Coriolus versicolor in China, has also been widely used as an anti-cancer and immunomodulatory agent. Although the mechansim of their antitumor action is still not completely clear, these polysaccharides and polysaccharide-protein complexes are suggested to enhance cell-mediated immune responses in vivo and in vitro and act as biological response modifiers. Potentiation of the host defense system may result in the activation of many kinds of immune cells that are vitally important for the maintenance of homeostasis. Polysaccharides or polysaccharide-protein complexes are considered as multi-cytokine inducers that are able to induce gene expression of vaious immunomodulatory cytokines and cytokine receptors. Some interesting studies focus on investigation of the relationship between their structure and antitumor activity, elucidation of their antitumor mechanism at the molecular level, and improvement of their various biological activities by chemical modifications.

PMID: 10702635 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/10702635

Dr. Mark Flannery Joins inLife LLC’s Board as Medical Advisor

Irvine, California inLife, LLC distributors of science-based Health & Wellness products, today announced Dr. Mark Flannery joins inLife’s Board as Medical Advisor. Dr. Flannery, who specializes in the treatment of autoimmune disorders and chronic illness using advanced nutritional therapies is a Diplomate of the College of Clinical Nutrition, a Diplomate of the Chiropractic Board of Clinical Nutrition, and a Certified Nutrition Specialist by the Certification Board for Nutrition Specialists, today joins inLife to bring awareness and enlightenment to the public of inLife’s new immunological nutritional supplement, inForce Immune Builder.

Dr. Flannery who assists his patients in achieving their optimal health by focusing on correcting the imbalances in their physiology says, “After much research and analization of inLife inForce Immune Builder’s main ingredient Coriolus versicolor, I am very proud to be part of a company that is on the verge of helping many, many people realize their true health potential. In reviewing the research and viewing many of the testimonials so far submitted to inLife I am convinced that inForce Immune Builder should be part of everyone’s daily nutritional routine.” Dr. Flannery will also soon be seen interviewed by Cristina Ferrare on inLife’s soon-to-be-viewed national infomercial about the science behind inForce Immune Builder.

About Coriolus Versicolor

The Coriolus Versicolor mushroom is one of the most widely studied supplements for its immune building properties. 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. Traditionally, the Coriolus versicolor mushroom (known as Yun-zhi or cloud mushroom in China) has been used in China for several thousand years because of its immune boosting capabilities. In the 1980s, Dr. Yang conducted further studies and was able to isolate a much more potent strain using a different, alcohol-based extraction process. The result was Polysaccharopeptide or PSP. In the United States, top-ranked hospital and research institutes have reported that Coriolus versicolor helps boost the body’s immune systems 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.

inLife Immune Builder with PSP and PSK

inLife offers Coriolus versicolor as a Daily Dietary Supplement in capsule form to help maintain and stimulate the body’s immune system. Coriolus versicolor and its high-potency extracts, 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 Polysaccharopeptide (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).

About inLife, LLC

Founded in 2007, inLife has been very successful in bringing to 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.

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Founded in 2007, inLife has been very successful in bringing to market products that have efficacies that are soundly based on scientific research. For further details on inForce, journalists may contact Thomas Kiklas directly at 949-648-2525.

Click here to download this press release.

Susceptibility of natural killer (NK) cells to reactive oxygen species (ROS) and their restoration by the mimics of superoxide dismutase (SOD).

Nakamura K, Matsunaga K.

Department of Biochemistry, Kitasato University School of Medicine, Kanagawa, Japan.

Abstract

Natural killer (NK) cells are susceptible to reactive oxygen species (ROS), and lose the activity by the effects of ROS. Cancer bearing hosts usually suffer from oxidative stress (OS), and the NK-activity decreases to a significantly lower level than normal controls. Superoxide dismutase (SOD)-mimicking substances, such as protein-bound polysaccharide of Coriolus versicolor (Fr) QUEL (PSK) and iron-chelating chlorine e6-Na (FeCNa), can restore the NK-activity of cancer bearing hosts, when collaborating with catalase. Incorporation of 3H-thymidine by ROS-treated NK-cells is not affected, indicating that these cells are still active in the nucleic acid metabolism. Intraperitoneal administration of anti-Asialo GM1 antibody extinguished the NK-activity. NK-cells affected by ROS lost the adherence to target cancer cells in both in vitro and in vivo. ROS may change the surface charge of NK-cells to anionic, resulting in an inability of adhesion to target cancer cells which usually show the negative surface charge.

PMID: 10850363 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/10850363

Cell growth and gene modulatory activities of Yunzhi (Windsor Wunxi) from mushroom Trametes versicolor in androgen-dependent and androgen-insensitive human prostate cancer cells.

Hsieh TC, Wu JM.

Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA.

Abstract

The incidence of prostate cancer varies greatly throughout the world; it is highest in African-Americans and lowest in the Asian populations of China, India, and Japan. Geographical differences in both prevalence of latent prostate cancer and mortality have been postulated to be influenced by diverse tumor-promoting and protective factors, both environmental and dietary. Prostate cancer is a tumor with an extremely long latency; the pattern of prostate tumorigenesis, in terms of the display and sequence of appearance of particular molecular or biochemical features, or morphological changes, characterizing different stages of the carcinogenic process, is expected to be heterogeneous. Some insights into tumor heterogeneity and progression can be obtained from studies using cell lines, particularly those derived from different anatomical sites. The present study aims to investigate whether hormone-responsive LNCaP and androgen-refractory JCA-1, PC-3, and DU-145 prostate cancer cells are responsive to Yunzhi (YZ), a proprietary dietary supplement prepared from extracts of Trametes versicolor, also known as Coriolus versicolor (a mushroom consumed by Chinese for its purported health benefits), and to elucidate its mechanism of action. Ethanolic extracts (70%) of YZ significantly reduced LNCaP cell growth, down-regulated the levels of secreted PSA, but had less effects on the expression of intracellular PSA and did not affect levels of the androgen receptor. In androgen-unresponsive prostate cancer cells, YZ had a much less pronounced suppressive effect on proliferation of PC-3 and DU-145 cells, compared to LNCaP, and was inactive against JCA-1 cells. Western blot analyses show that the expression of Rb, a key regulatory protein in G1/S transition, and PCNA, integrally involved in mammalian cell DNA replication, were significantly reduced by treatment with YZ in PC-3 and DU-145 cells, respectively. In contradiction, none of these biochemical parameters were affected in JCA-1 cells under identical treatment conditions. Further analysis shows that YZ increased the levels of signal transducer and activator family of transcription factors STAT 1 and STAT 3 in JCA-1 and not LNCaP cells. The greater sensitivity of LNCaP cells to this polysaccharopeptide raises the possibility that YZ may be considered as an adjuvant therapy in the treatment of hormone responsive prostate cancer; additionally, it may have chemopreventive potential to restrict prostate tumorigenic progression from the hormone-dependent to the hormone-refractory state.

PMID: 11115542 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/11115542

Anticancer effects and mechanisms of polysaccharide-K (PSK): implications of cancer immunotherapy.

Fisher M, Yang LX.

Radiobiology Laboratory, St. Mary’s Medical Center, California Pacific Medical Center Research Institute, San Francisco 94118, USA.

Abstract

Polysaccharide-K (polysaccharide-Kureha; PSK), also known as krestin, is a unique protein-bound polysaccharide, which has been used as a chemoimmunotherapy agent in the treatment of cancer in Asia for over 30 years. PSK and Polysaccharopeptide (PSP) are both protein-bound polysaccharides which are derived from the CM-101 and COV-1 strains of the fungus Coriolus versicolor by Japanese and Chinese researchers, respectively. Both polysaccharide preparations have documented anticancer activity in vitro, in vivo and in human clinical trials, though PSK has been researched longer and has therefore undergone more thorough laboratory, animal and clinical testing. Several randomized clinical trials have demonstrated that PSK has great potential as an adjuvant cancer therapy agent, with positive results seen in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunotherapy or biological response modifier (BRM). BRMs potentially have the ability to improve the “host versus tumor response,” thereby increasing the ability of the host to defend itself from tumor progression. The mechanisms of biological response modification by PSK have yet to be clearly and completely elucidated. Some studies suggest that PSK may act to increase leukocyte activation and response through up-regulation of key cytokines. Indeed, natural killer (NK) and lymphocyte-activated killer (LAK) cell activation has been demonstrated in vivo and in vitro, and recent genetic studies reveal increased expression of key immune cytokines in response to treatment with PSK. An antimetastatic action of PSK has also been demonstrated and is perhaps attributed to its potential to inhibit metalloproteinases and other enzymes involved in metastatic activity. PSK has also been shown to cause differentiation of leukemic cells in vitro, and this effect has been attributed to induction of differentiation cytokines. PSK has further been shown to have antioxidant capacity which may allow it to play a role as a normal tissue chemo- and radio-protector when used in combination with adjuvant or definitive chemotherapy and/or radiotherapy in the treatment of cancer, while it may also enable it to defend the host from oxidative stress. Interestingly, studies have also shown that PSK may actually inhibit carcinogenesis by inhibiting the action of various carcinogens on vulnerable cell lines. This action of PSK may play a role in preventing second primary tumors when an inducing agent, such as tobacco or asbestos, is suspected and may also prevent second malignancies due to the carcinogenic effects of radiotherapy and cytotoxic chemotherapy. Another very important aspect of chemoimmunotherapy, in general is that it may be used on debilitated patients such as those with AIDS and the elderly who might otherwise be denied potentially helpful adjuvant cytotoxic chemotherapy. Further determination of the mechanisms of these anti-cancer, immunostimulating and biological response modifying effects of PSK as well as of other protein-bound polysaccharides is certainly warranted. Indeed, with modern cellular and molecular biology techniques, a better understanding of the specific molecular effects of PSK on tumor cells as well as leukocytes may be determined. Much of the research that has been done on PSK is outlined in this paper and may serve as a foundation toward determining the mechanisms of action of this and other protein-bound polysaccharides in the treatment of cancer. This information may open new doors in the development of novel strategies for the treatment of malignancies using adjuvant immunotherapy in combination with surgery, chemotherapy and/or radiotherapy.

PMID: 12168863 [PubMed – indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/12168863

Biological activity of 4-acetyltropolone, the minor component of Thujopsis dolabrata SIeb. et Zucc. hondai Mak.

Morita Y, Matsumura E, Tsujibo H, Yasuda M, Okabe T, Sakagami Y, Kumeda Y, Ishida N, Inamor Y.

Osaka Organic Chemical Industry, Ltd, Kashiwara, Japan.

Abstract

4-Acetyltropolone, a minor component of Thujopsis dolabrata SIEB. et Zucc. hondai MAKINO, showed antimicrobial activity against various microorganisms including wood-rotting fungi, a phytogrowth-inhibitory effect with chlorophyll biosynthesis inhibition, cytotoxic effect and inhibitory activity on metalloproteases. This compound had strong antifungal activity on Daedalea dickinsii IFO-4979 [minimum inhibitory concentration (MIC): 0.2 microg/ml] and Coriolus versicolor IFO-4940 (MIC: 0.39 microg/ml). Its cytotoxic effect at 20.0/microg/ml on human stomach cancer KATO-III and Ehrich’s ascites carcinoma was stronger than those of podophyllotoxin, vincristine and vinblastine, the anticancer agents isolated from higher plants and used clinically. This compound also had potent antibacterial activity against Staphylococcus epidermidis IFO-12993, its MIC being 1.56 microg/ml. However, other biological activities of 4-acetyltropolone were lower than those of hinokitiol which is the main component of this plant, suggesting that the contribution of the acetyl group at C-4 to biological activity is smaller than that of the isopropyl group at that position. The acute toxicity of 4-acetyltropolone (LD50: 335.2 mg/kg) to mice was much lower than that of hinokitiol (LD50: 191 mg/kg).

PMID: 12186430 [PubMed – indexed for MEDLINE]Free Article

http://www.ncbi.nlm.nih.gov/pubmed/12186430