Immunomodulation Through Beta-D-glucan in Chemically-induced Necrotizing Pancreatitis.

BACKGROUND: Although the ability of ß-D-glucan and monophosphoryl lipid A (MPLA) to modulate immune responses has been studied in human primary cells, their effect on sterile inflammation models such as necrotizing pancreatitis has never been investigated. MATERIALS AND METHODS: 85 male New Zealand rabbits were assigned into following groups: A: control, B: pretreatment with ß-D-glucan 3 d before pancreatitis, C: pretreatment with MPLA 3 d before pancreatitis, D: pretreatment with ß-D-glucan and laminarin 3 d before pancreatitis, E: treatment with ß-D-glucan 1 d after pancreatitis, and F: MPLA 1 d after pancreatitis. Pancreatitis was induced by sodium taurocholate injection into the pancreatic duct and parenchyma. Survival was recorded for 21 d. On days 1, 3, and 7, blood was collected for amylase measurement. Peripheral blood mononuclear cells were isolated and stimulated for tumor necrosis factor alpha and interleukin 10 production. Pancreatic necrosis and tissue bacterial load were assessed. RESULTS: 21-d survival was prolonged after pretreatment or treatment with ß-D-glucan; this benefit was lost with laminarin administration. At sacrifice, pancreatic inflammatory alterations were more prominent in the control group. Bacterial load was lower after pretreatment or treatment with ß-D-glucan and MPLA. Tumor necrosis factor alpha production from stimulated peripheral blood mononuclear cells was significantly decreased, whereas interleukin 10 production remained unaltered after pretreatment or treatment with ß-D- glucan. CONCLUSIONS: ß-D-glucan reduces mortality of experimental pancreatitis in vivo. This is mediated through attenuation of cytokine production and prevention of bacterial translocation.

Proteoglycan-4 is correlated with longer survival in HCC patients and enhances sorafenib and regorafenib effectiveness via CD44 in vitro.

Sorafenib and regorafenib administration is among the preferential approaches to treat hepatocellular carcinoma (HCC), but does not provide satisfactory benefits. Intensive crosstalk occurring between cancer cells and other multiple non-cancerous cell subsets present in the surrounding microenvironment is assumed to affect tumor progression. This interplay is mediated by a number of soluble and structural extracellular matrix (ECM) proteins enriching the stromal milieu. Here we assess the HCC tumor expression of the ECM protein proteoglycan 4 (PRG4) and its potential pharmacologic activity either alone, or in combination with sorafenib and regorafenib. PRG4 mRNA levels resulted strongly correlated with increased survival rate of HCC patients (p = 0.000) in a prospective study involving 78 HCC subjects. We next showed that transforming growth factor beta stimulates PRG4 expression and secretion by primary human HCC cancer-associated fibroblasts, non-invasive HCC cell lines, and ex vivo specimens. By functional tests we found that recombinant human PRG4 (rhPRG4) impairs HCC cell migration. More importantly, the treatment of HCC cells expressing CD44 (the main PRG4 receptor) with rhPRG4 dramatically enhances the growth-limiting capacity of sorafenib and regorafenib, whereas not significantly affecting cell proliferation per se. Conversely, rhPRG4 only poorly potentiates drug effectiveness on low CD44-expressing or stably CD44-silenced HCC cells. Overall, these data suggest that the physiologically-produced compound PRG4 may function as a novel tumor-suppressive agent by strengthening sorafenib and regorafenib effects in the treatment of HCC.

Endocan regulates acute lung inflammation through control of leukocyte diapedesis.

Acute respiratory distress syndrome is a severe form of respiratory failure, occurring in up to 20% of patients admitted to the intensive care unit with sepsis. Dysregulated leukocyte diapedesis is a major contributor to acute respiratory distress syndrome. Endocan is a circulating proteoglycan that binds to the leukocyte integrin leukocyte functional antigen-1 and blocks its interaction with its endothelial ligand, ICAM-1. The objective of this study was to evaluate the role of endocan in the control of acute lung inflammation. In vitro, endocan inhibited human leukocyte transendothelial migration as well as ICAM-1-dependent migration but had a very mild effect on ICAM-1-dependent adhesion. Endocan also acted as an inhibitor of transendothelial migration of mouse leukocytes. The effect of systemic administration of recombinant human endocan was assessed in a model of acute lung inflammation in BALB/c mice. Treatment with endocan 1 h after intratracheal LPS challenge reduced the alveolar inflammatory response, diminished histological features of acute lung injury, and improved respiratory function. These results highlight the anti-inflammatory role of human endocan and its protective effect against acute lung injury.NEW & NOTEWORTHY We show here that endocan inhibits ICAM-1-dependent human leukocyte transendothelial migration and ICAM-1-dependent adhesion. We also found that in BALB/c mice with tracheal LPS-induced acute lung injury treatment with recombinant human endocan reduces lung inflammation, notably through reduction of neutrophilic recruitment, and restores normal lung function. These results confirm the hypothesis that human endocan may have a protective effect against acute lung inflammation.

Biomimetic proteoglycans can molecularly engineer early osteoarthritic cartilage in vivo.

Biomimetic proteoglycans (BPGs) have the potential to treat osteoarthritis (OA) given that these molecules mimic the structure and properties of natural proteoglycans, which are significantly reduced in OA. We examined the effects of BPGs injected into the intra-articular space in an in vivo OA rabbit knee model and evaluated the effect on histological response, joint friction, and BPG distribution and retention. Rabbits underwent ACL transection to create an arthritic state after 5 weeks. OA rabbits were treated with BPGs or Euflexxa® (hyaluronic acid) intra-articular injections. Non-OA rabbits were injected similarly with BPGs; contralateral joints served as controls. The progression of OA and response to injections were evaluated using Mankin and gross grading systems indicating that mild OA was achieved in operated joints. The coefficient of friction (COF) of the intact knee joints were measured using a custom pendulum friction apparatus, showing that OA joints and OA + Euflexxa® joints demonstrated increased COF than non-operated controls, while BPG-injected non-OA and OA + BPGs were not significantly different from non-OA controls. Injected fluorescently labeled BPGs demonstrated that BPGs diffused into cartilage with localization in the pericellular region. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:403-411, 2019.

Spore powder of Ganoderma lucidum for the treatment of Alzheimer disease: A pilot study.

BACKGROUND: This study explored the feasible efficacy and safety of the Spore Powder of Ganoderma Lucidum (SPGL) for treating patients with Alzheimer disease (AD). METHODS: Forty-two eligible patients with AD were recruited. These patients were randomly allocated to an intervention group and a control group equally. The patients in the intervention group underwent SPGL, whereas the subjects in the control received placebo. All patients were treated for a total of 6 weeks. The primary outcome was measured by Alzheimer's disease Assessment Scale-Cognitive (ADAS-cog). The secondary outcomes were measured by the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) and Neuropsychiatric Index (NPI). The adverse events were also recorded during the treatment period. RESULTS: At the end of the treatment, GLSP did not show more encouraging outcomes in symptoms improvement, measured by the ADAS-cog (P = .31), and NPI (P = .79); and quality of life enhancement, measured by the WHOQOL-BREF (physical, P = .62; psychological, P = .69; social relationships, P = .75; environment, P = .82; overall quality of life, P = .74), compared with the control group. In addition, all adverse events were mild, and no significant differences were found between 2 groups. CONCLUSION: The results of this study did not find the promising efficacy of SPGL for the treatment of AD after 6-week treatment. It may be because of the relative short-term of intervention. Future clinical trials with larger sample size and longer treatment period are urgently needed.

Preclinical Animal Studies of Intravesical Recombinant Human Proteoglycan 4 as a Novel Potential Therapy for Diseases Resulting From Increased Bladder Permeability.

OBJECTIVE: To test in an animal model the hypothesis that recombinant human proteoglycan 4 (rhPRG4; lubricin), a highly O-glycosylated mucin-like glycoprotein, may be a novel surface-active therapeutic for treating bladder permeability with comorbid bowel permeability. Previously we showed that inducing bladder permeability in rats with dilute protamine sulfate (PS) produced colonic permeability and visceral hypersensitivity, suggesting increased bladder permeability could represent an etiologic factor in both interstitial cystitis-bladder pain syndrome and irritable bowel syndrome. METHODS: We used an animal model of catheterized ovariectomized female rats instilled intravesically with 1 mg/mL PS for 10 minutes that after 24 hours were treated with 1.2 mg/mL lubricin or with vehicle alone. After 24 hours the bladder and colon were removed and permeability assessed electrophysiologically with the Ussing chamber to measure the transepithelial electrical resistance. A second set of rats was treated identically, except permeability was assessed on day 3 and on day 5 using contrast-enhanced magnetic resonance imaging with gadolinium diethylenetriamine penta-acetic acid instilled into the bladder. RESULTS: Intravesical lubricin reversed bladder permeability induced by PS and prevented the concomitant increase in permeability induced in the bowel (organ crosstalk). The protective effect was confirmed with magnetic resonance imaging, and because individual rats could be followed over time, the impermeability of the bladder restored by rhPRG4 remained for 5 days. CONCLUSION: These data indicate that instillation of rhPRG4 into a permeable bladder can restore its normally impermeable state, and that the effect lasts for 5 days and also prevents bowel symptoms often comorbid with interstitial cystitis-bladder pain syndrome.

N-acetyl glucosamine and proteoglycan containing supplement improves the locomotor functions of subjects with knee pain.

The aim of this study was to investigate the effect of N-acetyl glucosamine and proteoglycan-containing supplement (NGPS) on knee pain and locomotor functions in middle-aged and elderly persons with knee pain. An open trial was conducted on 19 subjects suffering from knee pain. The subjects, aged (55.6 ± 6.9) years, were given the NGPS tablets, which they must take 3 times per day, that contain 526.5 mg of N-acetyl glucosamine (GlcNAc) and 33.6 mg of proteoglycan for 12 weeks. Subjective pain was evaluated using the Visual Analog Scale (VAS), while the function of the knee with regard to daily operation was evaluated using the Japanese Knee Osteoarthritis Score (JKOM). Walking, stair-climbing and swelling were evaluated using the Japanese Orthopedic Association Score (JOA). These items were evaluated at a baseline, and after 4, 8, and 12 weeks of NGPS treatment. The VAS scores at 8 (p = 0.004) and 12 (p < 0.001) weeks were significantly lower than that at the baseline. The JKOM total score was significantly lower at 8 and 12 weeks (p = 0.001) than that at the baseline. The JOA score in the more painful side of the leg was significantly higher at 12 weeks (p = 0.002) than that at the baseline. The present study reveals that intake of NGPS is effective for relieving knee pain and improving knee function when walking or climbing stairs, swelling and bending or stretching.

Immunochemotherapy benefits in gastric cancer patients stratified by programmed death-1 ligand-1.

BACKGROUND: Effectiveness of protein-bound polysaccharide K (PSK) during adjuvant chemotherapy in gastric cancer patients expressing programmed death-1 ligand 1 (PD-L1) has not been investigated. Investigating this might help in triaging candidates eligible to immunochemotherapy. MATERIALS AND METHODS: In total, 918 patients with stages II and III gastric cancer, undergoing curative gastrectomy, and receiving adjuvant chemotherapy were enrolled in a prospective database, and the patients were retrospectively reviewed. We classified those patients into four cohorts stratified by PD-L1 expression and PSK administration, namely PD-L1, PSK (-,+); PD-L1, PSK (-,-); PD-L1, PSK (+,+); and PD-L1, PSK (+,-). In addition, another independent cohort of 20 patients undergoing radical gastrectomy was prospectively recruited to check their immunological cells of sera before and 2 mo after PSK administration. RESULTS: PSK treatment was an independent prognostic factor for patient's overall survival (P = 0.020), whereas PD-L1 expression per se was not. Administration of PSK prolonged patient survival in stages IIIA and IIIB (P = 0.031) but not in stage II or stage IIIC. Patients with negative expression of PD-L1, treated with PSK had longer survival than those not treated with PSK (P = 0.033). PSK did not affect the survival of patients with positive expression of PD-L1, (P = 0.421). The percentages of natural killer and natural killer T (NKT) cells, but not Th1, Th17, Treg, or IFN-γ+/CD8+ T cells, were significantly increased in PD-L1 (-) patients treated with PSK. However, these findings were not evident in PD-L1 (+) patients. CONCLUSIONS: PSK treatment preferentially confers a survival gain for patients with stage IIIA/IIIB gastric cancer, especially in the PD-L1 (-) subpopulation.

Reduction of friction by recombinant human proteoglycan 4 in IL-1α stimulated bovine cartilage explants.

A boundary lubricant attaches and protects sliding bearing surfaces by preventing interlocking asperity-asperity contact. Proteoglycan-4 (PRG4) is a boundary lubricant found in the synovial fluid that provides chondroprotection to articular surfaces. Inflammation of the diarthrodial joint modulates local PRG4 concentration. Thus, we measured the effects of inflammation, with Interleukin-1α (IL-1α) incubation, upon boundary lubrication and PRG4 expression in bovine cartilage explants. We further aimed to determine whether the addition of exogenous human recombinant PRG4 (rhPRG4) could mitigate the effects of inflammation on boundary lubrication and PRG4 expression in vitro. Cartilage explants, following a 7 day incubation with IL-1α, were tested in a disc-on-disc configuration using either rhPRG4 or saline (PBS control) as a lubricant. Following mechanical testing, explants were studied immunohistochemically or underwent RNA extraction for real-time polymerase chain reaction (RT-PCR). We found that static coefficient of friction (COF) significantly decreased to 0.14 ± 0.065 from 0.21 ± 0.059 (p = 0.014) in IL-1α stimulated explants lubricated with rhPRG4, as compared to PBS. PRG4 expression was significantly up regulated from 30.8 ± 19 copies in control explants lubricated with PBS to 3330 ± 1760 copies in control explants lubricated with rhPRG4 (p < 0.001). Explants stimulated with IL-1α displayed no increase in PRG4 expression upon lubrication with rhPRG4, but with PBS as the lubricant, IL-1α stimulation significantly increased PRG4 expression compared to the control condition from 30.8 ± 19 copies to 401 ± 340 copies (p = 0.015). Overall, these data suggest that exogenous rhPRG4 may provide a therapeutic option for reducing friction in transient inflammatory conditions and increasing PRG4 expression. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:580-589, 2017.

Polysaccharide K and Coriolus versicolor extracts for lung cancer: a systematic review.

BACKGROUND: Polysaccharide K, also known as PSK or Krestin, is derived from the Coriolus versicolor mushroom and is widely used in Japan as an adjuvant immunotherapy for a variety of cancer including lung cancer. Despite reported benefits, there has been no English language synthesis of PSK for lung cancer. To address this knowledge gap, we conducted a systematic review of PSK for the treatment of lung cancer. METHODS: We searched PubMed, EMBASE, CINAHL, the Cochrane Library, AltHealth Watch, and the Library of Science and Technology from inception to August 2014 for clinical and preclinical evidence pertaining to the safety and efficacy of PSK or other Coriolus versicolor extracts for lung cancer. RESULTS: Thirty-one reports of 28 studies were included for full review and analysis. Six studies were randomized controlled trials, 5 were nonrandomized controlled trials, and 17 were preclinical studies. Nine of the reports were Japanese language publications. Fifteen of 17 preclinical studies supported anticancer effects for PSK through immunomodulation and potentiation of immune surveillance, as well as through direct tumor inhibiting actions in vivo that resulted in reduced tumor growth and antimetastatic effects. Nonrandomized controlled trials showed improvement of various survival measures including median survival and 1-, 2-, and 5-year survival. Randomized controlled trials showed benefits on a range of endpoints, including immune parameters and hematological function, performance status and body weight, tumor-related symptoms such as fatigue and anorexia, as well as survival. Although there were conflicting results for impact on some of the tumor-related symptoms and median survival, overall most randomized controlled trials supported a positive impact for PSK on these endpoints. PSK was safely administered following and in conjunction with standard radiation and chemotherapy. CONCLUSIONS: PSK may improve immune function, reduce tumor-associated symptoms, and extend survival in lung cancer patients. Larger, more rigorous randomized controlled trials for PSK in lung cancer patients are warranted.

[Immunomodulatory and antitumor properties of polysaccharide peptide (PSP)]. / Immunomodulujace i przeciwnowotworowe wlasciwosci polisacharydopeptydu (PSP)

Modern medicine successfully uses multiple immunomodulators of natural origin, that can affect biological reactions and support body's natural defense mechanisms including antitumor activities. Among them is a group of products derived from fungi, including schizophyllan, lentinan, polysaccharide Krestin (PSK), and polysaccharidepeptide (PSP). Present paper is focused on polysaccharidepeptide, which due to the negligible toxicity and numerous benefits for health, is increasingly used in China and Japan as an adjuvant in the treatment of cancer. PSP is a protein-polisaccharide complex with a molecular weight 100 kDa derived from Coriolus versicolor mushroom. The results of numerous studies and clinical trials confirm that it inhibits the growth of cancer cells in in vitro and in vivo settings as well as decreases cancer treatment-related adverse side effects such as fatigue, loss of appetite, nausea, vomiting, and pain. PSP is able to restore weakened immune response observed in patients with cancer during chemotherapy. Its anti-tumor effects seemed to be mediated through immunomodulatory regulation. PSP stimulates cells of the immune system, induces synthesis of cytokines such as interleukin-1ß (IL-1ß), IL-6 and tumor necrosis factor-α (TNF-α), eicosanoids including prostaglandin E2 (PGE2), histamine, reactive oxygen species and nitrogen mediators. There is a growing interest in understanding the mechanisms of PSP action. Because of its unique properties and safety, PSP may become a widely used therapeutic agent in the near future.

Nutrition in oncologic patients during antiblastic treatment.

Cancer may induce weight loss and cachexia, and cancer treatment may contribute to nutritional impairment. Here, we review the literature on the mechanisms of cancer cachexia and the pharmacological interventions both in use in clinical practice and currently under development. Based on this analysis, several nutritional proposals for cancer patients are suggested and the importance of good nutritional status in candidates for hematopoietic stem cell transplantation is highlighted.

Effect of a novel proteoglycan PTP1B inhibitor from Ganoderma lucidum on the amelioration of hyperglycaemia and dyslipidaemia in db/db mice.

Protein tyrosine phosphatase 1B (PTP1B) is implicated in the negative regulation of the insulin signalling pathway by dephosphorylating the insulin receptor (IR) and IR substrates. Ganoderma lucidum has traditionally been used for the treatment of diabetes in Chinese medicine; however, its anti-diabetic potency and mechanism in vivo is still unclear. Our previously published study reported a novel proteoglycan PTP1B inhibitor, named Fudan-Yueyang-Ganoderma lucidum (FYGL) from G. lucidum, with a half-maximal inhibitory concentration (IC50) value of 5·12 (sem 0·05) µg/ml, a protein:polyglycan ratio of 17:77 and 78 % glucose in polysaccharide, and dominant amino acid residues of aspartic acid, glycine, glutamic acid, alanine, serine and threonine in protein. FYGL is capable of decreasing plasma glucose in streptozotocin-induced diabetic mice with a high safety of median lethal dose (LD50) of 6 g/kg. In the present study, C57BL/6 db/db diabetic mice were trialed further using FYGL as well as metformin for comparison. Oral treatment with FYGL in db/db diabetic mice for 4 weeks significantly (P < 0·01 or 0·05) decreased the fasting plasma glucose level, serum insulin concentration and the homeostasis model assessment of insulin resistance. FYGL also controlled the biochemistry indices relative to type 2 diabetes-accompanied lipidaemic disorders. Pharmacology research suggests that FYGL decreases the plasma glucose level by the mechanism of inhibiting PTP1B expression and activity, consequently, regulating the tyrosine phosphorylation level of the IR ß-subunit and the level of hepatic glycogen, thus resulting in the improvement of insulin sensitivity. Therefore, FYGL is promising as an insulin sensitiser for the therapy of type 2 diabetes and accompanied dyslipidaemia.

Polysaccharide-K (PSK) in cancer--old story, new possibilities?

Polysaccharide-K (PSK, Krestin) is one of the most commonly used medicinal mushroom extracts with a long history as an additive in cancer therapy in Asia, especially in Japan. PSK has a documented anti-tumor activity both in vitro and in vitro, in various types of cancers, including colorectal, gastric, breast, liver, pancreatic, and lung cancer. Despite PSK having been studied for about 40 years as an immune modulator and biological response modifier, the mechanisms of action by PSK have not yet been clearly and completely elucidated. This review aims to provide an up-to-date account for the effects of PSK in cancer with the hope of thereby providing an increased understanding of the molecular mechanisms of PSK and also its potential as an additive in modern cancer therapy.

Role of substrates in diabetes therapy: stem cell differentiation and islet transplantation.

Type 1 diabetes affects more than a million people in the United States and many more across the world. While pharmaceutical interventions and insulin supplementation are the most commonplace treatment of diabetes, these are not essentially cures and can potentially lead to long-term complications. Transplantation of insulin-producing Islets of Langerhans from donor pancreas has been established as a promising alternative to diabetes therapy. While successful islet transplantation has the potential of providing a cure, the primary hurdles to be overcome for it to be clinically viable are the scarcity of donor islets and immune rejection of transplanted islets. Recent advances in stem cell culture and differentiation techniques have established stem cells as a likely source of transplantable islets. Different stem cell sources have been induced toward pancreatic differentiation using specific chemical perturbations along with use of specific substrates. An approach to overcoming the second hurdle of immune rejection of transplantable islets is to encapsulate the islets in specific biomaterials. In this review, we discuss the extensive use of various substrates for pancreatic differentiation of different stem cell sources, along with different biomaterial designs used for islet transplantation.

Goji (Lycium barbarum and L. chinense): Phytochemistry, pharmacology and safety in the perspective of traditional uses and recent popularity.

Since the beginning of this century, Goji berries and juice are being sold as health food products in western countries and praised in advertisements and in the media for well-being and as an anti-aging remedy. The popularity of Goji products has rapidly grown over the last years thanks to efficient marketing strategies. Goji is a relatively new name given to Lycium barbarum and L. chinense, two close species with a long tradition of use as medicinal and food plants in East Asia, in particular in China. While only L. barbarum is officinal, the fruit (fructus Lycii) and the root bark (cortex Lycii radicis) of both species are used in the folk medicine. We review here the constituents, pharmacology, safety, and uses of L. barbarum and L. chinense with consideration to the different parts of the plant. Investigations of the fruit have focused on proteoglycans, known as " Lycium barbarum polysaccharides", which showed antioxidative properties and some interesting pharmacological activities in the context of age related diseases such as atherosclerosis and diabetes. As to the root bark, several compounds have demonstrated a hepatoprotective action as well as inhibitory effects on the rennin/angiotensin system which may support the traditional use for the treatment of hypertension. While there are no signs of toxicity of this plant, two cases of possible interaction with warfarin point to a potential risk of drug interaction. In view of the available pharmacological data and the long tradition of use in the traditional Chinese medicine, L. barbarum and L. chinense certainly deserve further investigation. However, clinical evidences and rigorous procedures for quality control are indispensable before any recommendation of use can be made for Goji products.

Possible immunotherapeutic potentiation with D-fraction in prostate cancer cells.

BACKGROUND: Prostate cancer remains the most common malignancy among elderly men and the second leading cause of cancer death in the United States. Although several conventional therapies are currently available, they have a low efficacy and the more effective treatment modalities need to be established. Interferons (IFNs) are one of such options known as immunotherapy and demonstrated their antitumor effects on certain cancer types. Yet such antitumor activity should be improved or potentiated to have the satisfactory outcomes. In fact, combination therapy has been proposed as an alternative approach and is being underway in human and animal studies. Accordingly, we studied whether the combination of IFN-alpha and D-fraction (PDF), a bioactive mushroom extract, might potentiate anticancer activity of IFN-alpha in prostate cancer PC-3 cells in vitro. RESULTS: Potential effects of recombinant IFN-alpha(2b) (0-100,000 IU/ml), PDF (0-1,000 microg/ml), or their combinations were assessed on the growth of PC-3 cells at 72 h. Cell cycle analysis using a flow cytometer and Western blot analysis were performed to explore antiproliferative mechanism of these agents. The dose-dependent study showed that IFN-alpha(2b) up to 20,000 (20 K) IU/ml had no significant effects, but >60% growth reduction was attained 60%) down-regulated in IFN/PDF-treated cells. CONCLUSION: The combination of IFN-alpha(2b) (10 K IU/ml) and PDF (250 microg/ml) is capable of inducing a approximately 65% reduction in PC-3 cell growth. This appears to be due to a synergistic potentiation of two agents, leading to a G1 cell cycle arrest. Thus, it is conceivable that PDF may potentiate IFN-alpha(2b) activity, improving immunotherapy for prostate cancer.

Immunochemotherapy with PSK and fluoropyrimidines improves long-term prognosis for curatively resected colorectal cancer.

Long-term survival, which extends beyond 5 years, is a desired outcome for colorectal cancer patients. In the present study, we retrospectively compared the 10-year overall survival between the control group and the polysaccharide kureha (PSK) group and analyzed the factors influencing the prognosis. The control group was treated exclusively with oral fluoropyrimidines, whereas the PSK group was treated with fluoropyrimidines, given in conjunction with PSK for 24 months. The 10-year survival rates for the PSK group (81.9%) were significantly superior to those of the control group (50.6%). In Dukes' C cases, the 10-year overall survival rates for the PSK group were also significantly higher than those of the control group. In cases with lymphatic invasion graded ly2-ly3 or venous invasion graded v2-v3, the 10-year overall survival rates were 80.6% in the PSK group, which were significantly superior, compared to 25.9% in the control group. Analysis by Cox's proportional hazard model showed a significant difference between the control and PSK groups. These results indicate that postoperative adjuvant immunochemotherapy with PSK greatly improves prognosis at 10 years. On the basis of these results, we recommend postoperative adjuvant immunochemotherapy combined with PSK for patients with Dukes' C and in cases with ly2-ly3 or v2-v3 invasion.

Immunoregulatory and anti-tumor effects of polysaccharopeptide and Astragalus polysaccharides on tumor-bearing mice.

The aim of this study was to determine whether polysaccharopeptide (PSP) and Astragalus polysaccharides (APS) can be combined together as a new complex prescription (PSP + APS) for aiding adriamycin (AMD) chemotherapy. Ehrlich's ascites carcinoma (EAC) was used to establish a solid tumor model in Kunming mice. Immunocytochemical and immunohistochemical analysis were employed to detect the immunoregulatory and anti-tumor effects of EAC bearing mice after 30 days of administration with PSP and APS. PSP and PSP + APS could significantly increase the percentage of CD3(+) and CD4(+) T-lymphocytes, the ratio of CD4(+)/CD8(+), and the expression of IL-2/IL-2R in spleen and Bax in tumor tissue, but led to a diminution of Bcl-2 and CDK4 in tumor tissue compared with those of control group. In addition, PSP +APS could restore the immunological effects against AMD-induced immunosuppression, such as the subset of leukomonocyte, the expression of IL-2/IL-2R in the spleen, and the thymus index. These findings suggest that the immunomodulatory and anti-cancer effects of this new formula (PSP+APS) were better than those of PSP alone, and also could resist immunosuppression induced by AMD.