Krestin Research Articles

Polysaccharide-K (PSK) may suppress surgical stress-induced metastasis in rat colon cancer

We previously demonstrated that hepatic ischemia and reperfusion (I/R) injury increased liver metastasis and cancer growth of RCN-H4 cells. Using a rat model of hepatic I/R-induced liver metastasis, we investigated the metastasis-suppressing effect of polysaccharide-K (PSK), a biological response modifier composed of protein-bound polysaccharide. Fischer rats underwent 60 min of 70% partial hepatic ischemia. After 60 min of reperfusion, rat colon adenocarcinoma cells (RCN-H4) were inoculated intrasplenically. PSK was administered orally before I/R, after I/R, or before and after I/R. The weights of metastatic lesions of the liver or the numbers of liver metastatic nodules were determined on day 21. The effect of PSK on angiogenesis was studied by a rat cornea model using RCN-H4 cells or a vascular endothelial growth factor (VEGF)-containing pellet and an in vitro VEGF-induced endothelial cell migration assay. PSK administration significantly (p < 0.05) suppressed the I/R-induced increase in hepatic metastasis of RCN-H4 cells. The suppression of I/R-promoted metastasis was observed irrespective of the timing of administration. Furthermore, PSK significantly suppressed angiogenesis induced by RCN-H4 cells (p < 0.05) and the VEGF pellet (p < 0.01). PSK significantly suppressed the VEGF-induced migration of vascular endothelial cells (p < 0.05). PSK may suppress metastasis induced by hepatic I/R. The suppression of angiogenesis by PSK may be one of the mechanisms of the inhibition of hepatic metastasis.

Anti-cancer compound from medicinal mushrooms

Various mushrooms have been used as folk medicine for long times, the higher Basidiomycetes have become a matter of great interest due to their diverse nutritional, medicinal, and pharmacological properties. 650 species and intraspecific taxa from 182 genera of higher Hetero- and Homo-basidiomycetes have been listed that contain biological active anti-tumor and immunostimulative polysaccharides. Recently, lentinan, shizophyllan and krestin have been accepted as immunoceuticals in several oriental countries. Polysaccharides present the highest capacity for carrying biological information since they have the greatest potential for structural variability. Immunoceutical compound offer hope for cancer patient. These substances are pro-homeostatic uniquely effective immune boosters, which pose no threat of autoimmune backlash. The enhancement or potentiation of host defense mechanisms has been recognized as a possible means of inhibiting tumor growth without harming the host. Antitumor polysaccharides isolated from mushrooms (fruit-body, submerged cultured mycelial biomass or liquid culture broth) are either water-soluble ?-D-glucans, ?-D-glucans with heterosaccharide chains of xylose, mannose, galactose, and uronic acid or; ?-D-glucan-protein complexes-proteoglycans. Certain terpenoids and their derivatives have been isolated from mushroom species have been shown cytotoxic and anti-cancer properties. The discovery and identification of new safe drugs, without sever side effects, has become an important goal of research in the biomedical sciences and mushrooms have shown that they can be an interesting goal for cancer research.

Helicobacter pylori infection as an independent prognostic factor for locally advanced gastric cancer with curative resection

4562 Background: A few studies reported the association between helicobacter pylori (HP) infection and better overall survival (OS) in resected gastric cancer patients (pts). Methods: We investigated the HP infection status and its association with clinicopathologic characteristics in 210 locally advanced gastric cancer patients (stage IB: 18, II: 61, IIIA: 62, IIIB: 31, IV: 38) who underwent adjuvant chemotherapy (CTX) after curative resection (≥D2 dissection). HP infection status in hematoxlin and eosin stained peritumoral tissue was graded according to the updated Sydney System and categorized as HP(-) (normal or mild infection) and HP(+) (moderate or marked infection) (Am J Surg Pathol 20:1161, 1996). Twenty-two pts received 5-FU, doxorubicin (DOX) CTX (5- FU 500 mg/m2 weekly for 36 wks, DOX 40 mg/m2 q 3 weeks x 12) with or without OK432, while 188 pts underwent 5-FU, mitomycin-C (MMC), and polysaccharide-K (PSK) CTX (5-FU 500 mg/m2 weekly for 24 wks, MMC 8 mg/m2 q 6 wks x 4, PSK 3 g/day for 16 wks) (Br J Cancer 84:186, 2001, Hepatogastroenterol 54:290, 2007). Results: The median follow-up duration of survivors was 125 (107–155) months. HP (-) was significantly correlated with Bormann type IV, larger tumor size (&gt;5.5cm),and stage IIIB. In univariate analysis, patients with HP(-) (104 pts) demonstrated significantly poor 10-year OS compared with those with HP (+) (106 pts) (15.9% vs. 87.7%, p&lt;0.0001). HP(-) was associated with poor outcome in all stages except stage IB (p=0.075). In multivariate analysis, HP(-) was the most significant independent prognostic factor of poor OS (hazard ratio 9.646, 95% CI 5.407–17.206, p&lt;0.0001) followed by advanced stage (p=0.032), Bormann type IV (p=0.037) and old age (p=0.015). Conclusions: HP infection status seems to have strong prognostic significance in locally advanced gastric cancer. HP (-) pts may need intensified adjuvant treatment and careful follow-up. No significant financial relationships to disclose.

The NKG2D expression on CD8+ T cells and the efficacy of polysaccharide K (PSK) in gastric cancer

3065 Some studies suggest that the immunoreceptor NKG2D expression on CD8+ T cells is down-regulated and this reduction may be involved in immune evasion in cancer patients. The present study was designed to investigate NKG2D expression on CD8+ T lymphocytes and its relationship to immune evasion in gastric cancer patients. NKG2D expression on both circulating and tumor-infiltrating CD8+ T cells was evaluated by multicolor flow cytometry. Soluble MHC class I chain-related gene A (MICA) in the sera was quantitated by ELISA. Transwell experiments were carried out to determine the effect of cancer cells on NKG2D expression. NKG2D expression on circulating CD8+ T cells was down-regulated and significantly correlated with IFN-gamma production in gastric cancer patients (r = 0.68; P = 0.007). NKG2D expression was closely related to undifferentiated cancer (P = 0.021) as was the depth of invasion (P = 0.012). There was no difference in soluble MICA between gastric cancer patients and normal controls. NKG2D expression on CD8+ T cells was remarkably reduced in the tissue of gastric cancer compared with peripheral blood (P = 0.046). Complete removal of tumor by surgery restored NKG2D expression on CD8+ T cells (P = 0.0049). Transwell experiments showed that this down-regulation was induced by direct contact between cancer cells and CD8+ T cells and that soluble factors did not affect the NKG2D expression. This phenomenon was blocked by the addition of anti-MICA antibodies. Furthermore, the NKG2D expression down-regulated by tumor cells was dose-dependently recovered by administration of non-specific immunopotentiator, polysaccharide K (PSK). Therefore, decreased NKG2D expression may be one of the key mechanisms responsible for immune evasion by tumors in gastric cancer. The NKG2D expression may be a promising biomarker for monitoring the efficacy of PSK. No significant financial relationships to disclose.

A prospective randomized trial comparing 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) versus UFT and PSK as adjuvant chemoimmunotherapy (CITX) for patients with locally advanced gastric cancer with curative resection

4581 Background: Adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, while adjuvant CITX showed improved outcome of patients (pts) compared to chemotherapy alone in a few trials. However, optimal chemotherapy regimen remains to be determined. We conducted a randomized trial comparing oral (PO) CITX with intravenous (IV) CITX in gastric cancer pts with curative resection. Methods: All enrolled pts underwent radical surgery with at least D2 dissection. After stratification for pathologic stage (IB or II vs. III) and primary tumor size (≤5 cm vs. >5 cm), pts were randomized to IV CITX (5-FU 500 mg/m2 weekly for 24 weeks, MMC 8 mg/m2 every 6 weeks x 4) or PO CITX (UFT 400–600 mg/day for 12 months). Pts in both arms received PSK 3 g/day PO for 4 months. The planned target number of pts was 368 to prove the non-inferiority of PO CITX compared to IV CITX in overall survival. Results: A total of 82 pts (stage IB: 6, II: 29, IIIA: 30, IIIB: 17; 44 in IV arm, 38 in PO arm) were enrolled between May 2002 and October 2005, when the trial was closed due to poor accrual. Pts characteristics were well balanced. With a median follow-up of 51 months (25–68 months) in survivors, there were no significant differences in 4- year disease-free survival (75% vs. 62%, p=0.195) and overall survival (76% vs. 70%, p=0.445) between IV and PO arms. No grade 4 toxicity was observed in both arms. IV arm demonstrated higher incidence of grade 2 or 3 neutropenia (79% vs. 52%, p=0.025), thrombocytopenia (19% vs. 0%, p=0.008), and vomiting (36% vs. 9%, p=0.013). Conclusions: Although accrual was well below that planned, the results of this trial suggest that PO CITX with UFT might have similar efficacy with lower toxicity profile compared with 5-FU and MMC CITX in adjuvant treatment for gastric cancer. No significant financial relationships to disclose.

Leukotriene B4 activates T cells that inhibit B-cell proliferation in EBV-infected cord blood–derived mononuclear cell cultures

Epstein-Barr virus (EBV)-specific cellular memory is not transferred from mother to child. Therefore, EBV-induced B-cell proliferation in in vitro-infected cord blood mononuclear cell cultures is not inhibited. However, by addition of immunomodulators, polysaccharide K (PSK) or truncated thioredoxin (Trx80) that activate monocytes, EBV-specific T-cell response could be generated in such cultures. Presently, we demonstrate that leukotriene B(4) (LTB(4)) is involved in the effect of the immunomodulators. LTB(4) was detected in the medium, and T-cell activation was compromised by addition of leukotriene biosynthesis inhibitors. Moreover, we found that LTB(4) added to infected cultures, which did not receive the immunomodulators, induced functional activation of the T cells. LTB(4) activated the monocytes and acted directly on the T cells. In consequence, addition of LTB(4) inhibited the EBV-induced proliferation of B lymphocytes. Specific cytotoxicity could be generated by restimulation of the T cells. The experiments showed successive stages of T-cell activation in acquisition of their immunologic effector function. This is orchestrated by complex cellular interactions, and autocrine loops mediated by soluble factors-here interferon (IFN)-gamma, interleukin (IL)-15, IL-12, and LTB(4). Importantly, the results indicate that endogenous LTB(4) can induce T-cell activation that inhibits the EBV-induced proliferation of B lymphocytes.

A prospective randomized trial comparing 5-fluorouracil (5-FU), mitomycin-C (MMC), and polysaccharide-K (PSK) versus UFT and PSK as adjuvant chemoimmunotherapy (CITX) for patients with locally advanced gastric cancer with curative resection

15074 Background: Adjuvant chemotherapy has demonstrated small but significant survival benefit in locally advanced gastric cancer in several meta-analyses, while adjuvant CITX showed improved outcome of patients (pts) compared to chemotherapy alone in a few trials. However, optimal chemotherapy regimen remains to be determined. We conducted a randomized trial comparing oral (PO) CITX with intravenous (IV) CITX in gastric cancer pts with curative resection. Methods: All enrolled pts underwent radical surgery with at least D2 dissection. After stratification for pathologic stage (IB or II vs. III) and primary tumor size (=5 cm vs. &gt;5 cm), pts were randomized to IV CITX (5-FU 500 mg/m2 weekly for 24 weeks, MMC 8 mg/m2 every 6 weeks x 4) or PO CITX (UFT 400–600 mg/day for 12 months). Pts in both arms received PSK 3 g/day PO for 4 months. The planned target number of pts was 368 to prove the non-inferiority of PO CITX compared to IV CITX in overall survival. Results: A total of 82 pts (stage IB: 6, II: 29, IIIA: 30, IIIB: 17; 44 in IV arm, 38 in PO arm) were enrolled between May 2002 and October 2005, when the trial was closed due to poor accrual. Pts characteristics were well balanced. With a median follow-up of 39 months (14–55 months) in survivors, there were no significant differences in 3-year disease-free survival (82% vs. 61%, p=0.302) and overall survival (84% vs. 79%, p=0.838) between IV and PO arms. No grade 4 toxicity was observed in both arms. IV arm demonstrated higher incidence of grade 2 or 3 neutropenia (79% vs. 52%, p=0.025), thrombocytopenia (19% vs. 0%, p=0.008), and vomiting (36% vs. 9%, p=0.013). Conclusions: Although accrual was well below that planned, the results of this trial suggest that PO CITX with UFT might have similar efficacy with lower toxicity profile compared with 5-FU and MMC CITX in adjuvant treatment for gastric cancer. No significant financial relationships to disclose.

Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curative resections of gastric cancer.

Non-specific immunopotentiators, such as polysaccharide K (PSK), also known as OK-432, induce anti-tumor effects via immunological responses. The efficacy of combination immunochemotherapy using these immunopotentiators has been examined by multiple previous studies. The survival benefits of immunochemotherapy for patients with curative resections of gastric cancers are not widely accepted. To clarify this issue, we performed a meta-analysis to evaluate the effect of immunochemotherapy on survival in patients with curative resections of gastric cancer. For this study, we compared the results of chemotherapy and immunotherapy using the biological response modifier PSK as an immunopotentiator. The meta-analysis included 8,009 patients from eight randomized controlled trials after central randomization. The overall hazard ratio for eligible patients was 0.88 (95% confidence interval, 0.79-0.98; P = 0.018) with no significant heterogeneity [chi (2)(8) for heterogeneity = 11.7; P = 0.16]. The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK improves the survival of patients after curative gastric cancer resection.

Purification and Partial Characterization of an Acidic Polysaccharide with Complement Fixing Ability from the Stems of Avicennia Marina

An acidic polysaccharide fraction that had high anticomplementary activity was isolated from the stems of Grey Mangrove in 0.15% yield. The final fractions was designated HAM-3-IIb-II. The polysaccharide fraction appeared to be homogenous by high performance size exclusion chromatography with an estimated molecular weight of 105 kDa. The isolated polysaccharide is more effective than polysaccharide K (PSK) in its anticomplementary activity at 58 microg/ml of PSK and 23 microg/ml of HAM-3-IIb-II that inhibit 50% of complement activity in the complement fixation assay. Structural studies indicated that HAM-3-IIb-II was rich in galacturonic acid along with arabinose, galactose and rhamnose, characterizing a pectin-type polysaccharide, which was also confirmed by FT-IR spectrum. The presence of rich neutral sugar side chains of arabinogalactans may have contributed to the expression of high activity. Traditionally, this mangrove plant is used for medicinal purposes and it appears to have some scientific applications.

Efficacy of adjuvant immunochemotherapy with polysaccharide k (PSK) for patients with curatively resected gastric cancer

14038 Background: An anti-tumor effect of non-specific immunomodulators, mainly PSK and OK-432, via an immunological response has been reported and combination immunochemotherapy has been examined. However, the survival benefit of immunochemotherapy for patients with curatively resected gastric cancer was unclear in the world. We performed a meta-analysis in order to evaluate the survival effect of immunochemotherapy employing a biological response modifier Polysaccharide K (PSK) in Japan. Methods: We reassessed by means of meta-analysis of data with central randomization from 5164 patients enrolled in Japanese eight clinical trials. In all eight trials patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoint was 5-year survival odds ratio. Data were analyzed by using a weighted average of the log odds ratios (using Peto’s method). Results: The 5-year odds ratio for all eligible patients was 0.88 (95% confidence interval: 0.78–0.98; p=0.021). There was a significant heterogeneity between the trials (p=0.016). Conclusions: The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve survival of patients with curatively resected gastric cancer. No significant financial relationships to disclose.

ECA39 is a novel distant metastasis-related biomarker in colorectal cancer.

To investigate the possible role of polysaccharide-K (PSK) -related markers in predicting distant metastasis and in the clinical outcome of colorectal cancer (CRC). Firstly, we used protein microarrays to analyze the in vitro expression profiles of potential PSK-related markers in the human colorectal adenocarcinoma cell line SW480, which carries a mutant p53 gene. Then, we investigated the clinical implications of these markers in the prognosis of CRC patients. ECA39, a direct target of c-Myc, was identified as a candidate protein affected by the anti-metastatic effects of PSK. Immunohistochemistry revealed that ECA39 was expressed at significantly higher levels in tumor tissues with distant metastases compared to those without (P<0.00001). Positive ECA39 expression was shown to be highly reliable for the prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, negative predictive value: 90%). A significantly higher cumulative 5-yr disease free survival rate was observed in the ECA39-negative patient group (77.3%) compared with the ECA39-positive patient group (25.8%) (P<0.05). Our results suggest that ECA39 is a dominant predictive factor for distant metastasis in patients with advanced CRC and that its suppression by PSK might represent a useful application of immunotherapy as part of a program of integrated medicine.

Efficacy of adjuvant immunochemotherapy with polysaccharide K for patients with curatively resected colorectal cancer: a meta-analysis of centrally randomized controlled clinical trials.

The benefits of immunochemotherapy employing the biological response modifier polysaccharide K (PSK) for patients with curatively resected colorectal cancer was reassessed by means of a meta-analysis of data with center randomization from 1,094 patients enrolled in three clinical trials. In all three trials, patients were followed up for at least 5 years after surgery and enrollment of the last patient and outcomes for standard chemotherapy were compared with those for chemotherapy plus PSK. The endpoints were overall survival and disease-free survival; and intent-to-treat analysis was performed without patient exclusion. Data were analyzed using the weighted average of the individual log hazard ratios. The overall survival risk ratio for all eligible patients was 0.71 (95% confidence interval (CI) : 0.55-0.90; P=0.006), and the disease-free survival risk ratio was 0.72 (95% CI: 0.58-0.90; P=0.003). The results of this meta-analysis suggest that adjuvant immunochemotherapy with PSK can improve both survival and disease-free survival of patients with curatively resected colorectal cancer.

A novel distant metastasis-related marker in colorectal cancer

9684 Background: Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. There is growing evidence that Polysaccharide-K (PSK), or Krestin (Sankyo Co., Tokyo, Japan), a mushroom ingredient, prevents distant metastases and improves survival rates by 10 to 20% in colorectal, gastric, esophageal, nasopharynx, lung, and breast cancers. We set out to investigate the possible role of PSK-related markers in predicting distant metastasis and clinical outcome in colorectal cancer (CRC) patients. Methods: To screen PSK-related markers, we analyzed expression profiles using protein microarrays in human colorectal adenocarcinoma cell lines, SW480 with a mutant p53gene and HCT116 with a wild-type p53 gene, and their clinical implication on the prognosis of CRC patients (n=35). Results: We screened ECA39 protein, a direct target for c-Myc regulation, as a candidate relating to anti-metastatic effects of PSK. In immunohistochemistry, ECA39 was significantly expressed in the tumor tissues with distant metastases compared to the ones without metastases (p<0.00001). Positive ECA39 expression showed high reliability for prediction of distant metastases (sensitivity: 86.7%, specificity: 90%, positive predictive value: 86.7%, and negative predictive value 90%). Conclusions: Our results suggest that ECA39 is a dominant predictor of distant metastasis in patients with advanced CRC and may be useful for the application of immunotherapy by integrated medicine. No significant financial relationships to disclose.

PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12

AbstractEpstein-Barr virus (EBV)–specific immunologic memory is not transferred from mother to child. In vitro infection of cord blood cells can therefore readily lead to the outgrowth of transformed B lymphocytes. We found that the immunomodulator polysaccharide K (PSK) or the mitogenic cytokine truncated thioredoxin (Trx80) inhibited the EBV-induced B-cell proliferation. Using signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) induction as a sign for T- and natural killer (NK) cell activation, we could follow it without any need for cell separation because neither macrophages nor B lymphocytes express SAP. The results suggest the following scenario: EBV infected and activated B lymphocytes. Upon interacting with these cells, T cells became posed for responding to cytokines produced by monocytes. Both PSK and Trx80, which is a secreted C-terminally truncated thioredoxin, activated the monocytes, which then produced cytokines in the presence of the primed T cells. PSK induced interleukin-15 (IL-15), while Trx80 induced IL-12 production. Both cytokines activated the T cells for function. Phosphatidylinositol 3–(PI 3)–kinase and reactive oxygen species (ROSs) were involved in the PSK-induced activation of monocytes. Restimulation of the cultures with EBV-transformed B cells generated specific cytotoxic activity.

Gene expression in response to anti-tumour intervention by polysaccharide-K (PSK) in colorectal carcinoma cells

Distant metastasis is one of the major problems in treatment for advanced colorectal cancer. Polysaccharide-K (PSK), or Krestin, a mushroom ingredient, has been used as a chemoimmunotherapeutic agent for the treatment of cancers in Asia for over 30 years. Some studies have reported that PSK prevent distant metastases and improve survival rates by 10-20% in colorectal cancer. However, the mechanism of the interrelated immunomodulatory and direct anti-cancer cell activities of PSK has yet to be elucidated. To investigate the direct effect, we used cDNA microarrays to analyse expression profiles in a human colorectal adenocarcinoma cell line, HCT116, containing the wild-type p53 gene. Expression of 453 genes was significantly altered (142 up-regulated and 311 down-regulated) after 96 h exposure to 500 microg/ml PSK. Under more stringent conditions, 9 genes were up-regulated and 36 down-regulated. We then examined the expression of candidate genes in two cell lines, HCT116, and SW480, a cell line with a mutant p53 gene. Our results suggest that PSK may augment anti-tumour action via genes including multidrug resistance protein 3 (MRP3), lymphotactin (Lptn), transgelin (TAGLN), and Pirin, without disturbing cell-cycle progression, and may deserve a large clinical trial in cancer therapy.

Immunomodulatory Effects of Low Dose cis-Diaminedichloroplatinum (Cisplatin) Combined with UFT and PSK in Patients with Advanced Colorectal Cancer

It is well known that cell-mediated immunity is suppressed in patients with neoplastic diseases. We have reported that soluble receptors for interleukin-2 (sIL-2R) and tumor necosis factor (sTNF-R1) are elevated in the serum of patients with advanced colorectal cancer. The presence of these soluble receptors and immunosuppressive cytokines, including interleukin-10 (IL-10), might be important in the mechanisms of immunosuppression. cis-Diaminedichloroplatinum (cisplatin) has been reported to immunomodulate, especially when used in low dose in combination with 5-Fluorouracil (5-FU). In this study, cisplatin and UFT, a form of uracil and tegafur which is a prodrug of 5-FU, were administered with immunomodulator Polysaccharide K (PSK) to ten patients with colorectal cancer, who showed distant metastasis in the liver or lung, and the serum levels of sIL-2R and sTNF-R1 and the production of γ-interferon (γ-INF) and interleukin-10 by peripheral blood mononuclear cells were measured. The serum concentrations of sIL-2R and the production of IL-10 were reduced (p<0.05) after 2 months of treatment. Thus, this combination appeared to have immunomodulative potential in patients with advanced colorectal cancer.

Usefulness of polysaccharide K (PSK) as postoperative adjuvant immunotherapy in patients with stage IV gastric cancer

Background. We investigated retrospectively the usefulness of polysaccharide K (PSK) administration for prolonging survival after noncurative resection in patients with stage IV gastric cancer who underwent surgery at our department.

The effects of proteoglycan on GALT in rats treated with TPN.

It is well known that total parenteral nutrition (TPN) causes atrophy of the intestinal mucosa, resulting in degeneration and atrophy of the gut-associated lymphoid tissues (GALT). This study was conducted to examine the suppressive effect of TPN on GALT in rats. Rats that received TPN alone for 2 weeks, i.e., the TPN group, showed a decreased number of Peyer's patches and thoracic duct lymphocytes (TDL), as well as atrophy. Conversely, those treated with TPN in combination with polysaccharide K (PSK) at a daily dose of 1000 mg/kg for 2 weeks, i.e., the PSK group, showed increases in the number of Peyer's patches and TDL and improvement in the TDL subsets compared with the TPN group. Immunohistological examination of the changes in immunocytes in GALT using monoclonal antibodies revealed increases in the production of the major histocompatibility complex (MHC)-I and (MHC)-II, helper T cells, and interleukin 2 (IL-2). These findings indicate that PSK improves GALT suppression induced by TPN.

Yun Zhi Polysaccharopeptide (PSP) and the General Aspects of Its Research

This paper briefly introduces the general aspects of a new type biolobical response modifier—PSP. The production material of polysaccharopeptide (PSP) is the deep layer cultivated mycelia of Cov-1 strain of Yun Zhi isolated by the methol of water extraction and alcoholic precipitation. Its chemical components are protein-bound polysaccharides. After the analyses of (superscript 1) H, (superscript 13) C nuclear magentic resonance, GCMS on-line and HPLC analysis, it has been proved that the polysaccharopeptide contains Glc., Gla., Man., and Xy1. in addition to Ara. and Rahmose. In the polysaccharide of PSP, the main content is β1-3 glycosidic bond and it is different from that of Japanese Krestin (PSK). The pharmacology proves that PSP can obviously resist immune suppression caused by tumor-bearing or chemotherapy, prevent the atrophy of thymus, activate NK and LAK cells and incresse the contents of γ-interferon, IL-2, IL-6, etc. The toxicology proves that even administering 50-100 times the normal clinical dosage to patients, the toxicity of PSP is equivalent to that of ordinary drinking water, either in the cure of acute and chronic hepatitis, hereditary, reproductive and second generation teratogenic toxicity. PSP can obviously kill the SPS of lung cancer and SMMU-7721 of liver cancer cells and there is no obvious harm at all on V79 of lung cells and on GZG of liver cells. Through 485 cases of random double-blind clinical experiments, it has been proved that PSP can obviously improve the clinical symptoms of stomach, lung and esophagus cancer patients, lower the toxic and side effects of chemo- and radio-therapy and raise the life quality of patients. The total effective rate is 82.96%.

Prophylactic intervention in radiation-leukemia-virus-induced murine lymphoma by the biological response modifier polysaccharide K.

Polysaccharide K (PSK) is a biological response modifier used for adjuvant immunotherapy of malignant diseases. We studied the potential applicability of PSK for preventing tumor progression using an experimental model of murine lymphoma. Mice inoculated with the radiation leukemia virus (RadLV) develop thymic lymphomas after a latency of 3-6 months. However, 2 weeks after virus inoculation, prelymphoma cells can already be detected in the thymus. We found that PSK treatment induced hyperresponsiveness to concanavalin A and heightened production of interleukin-2 (IL-2) and IL-4 in spleen cells of both control and prelymphoma mice. The response was transient and was accompanied with a dominant usage of T cells expressing V beta 8, but other T cell subsets were also stimulated by PSK. T lymphoma cells expressing V beta 8.2 underwent apoptosis when incubated with PSK. Treatment of RadLV-inoculated mice with PSK delayed the onset of overt lymphoma (and mortality) but could not protect the mice from the disease. Combined treatment with PSK and a RadLV-specific immunotoxin prevented synergistically the progression of the prelymphoma cells to frank lymphoma. The results suggest that PSK contains a superantigen-like component that selectively activates V beta 8+ T cells. Its administration prelymphoma mice interfered with the process of lymphoma progression.