Biomedical subjects

C Yoshikumi

Publications and source records attributed to C Yoshikumi.

At least 19 recordsLinked to original sources

PubMed1992

Effects of biological response modifiers with different modes of action used separately and together on immune responses in mice with syngeneic tumours.

The effect of a protein-bound polysaccharide (PSK) obtained from cultured mycelia of the Basidiomycetes Coriolus versicolor on activities involved in the host defence mechanism of C57BL/6 mice bearing adenocarcinoma 755 was compared with that of live bacille Calmette-Guérin (BCG). Delayed footpad reaction, the activity of splenic natural killer cells and interferon production induced by concanavalin A in splenic cells of healthy mice were little affected by PSK, but in mice bearing tumours PSK prevented the tumour-induced reduction in these activities. Live BCG augmented these activities in healthy mice but had little effect on the reduction of activities induced by a tumour. The immunosuppressive activity of the serum of tumour-bearing mice was reduced by PSK administration; live BCG did not have this effect. The combined use of live BCG and PSK improved these activities in the host, with synergistic increases in the antitumour effect. These results suggest that the combined use of live BCG and PSK, which have different modes of action, may be useful in the treatment of cancer.

Adjuvants, Immunologic↗

PubMed1992

Enhancement of effector cell activities in mice bearing syngeneic plasmacytoma X5563 by a biological response modifier, PSK.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from Coriolus versicolor of basidiomycetes, on antitumor immunity in tumor-bearing mice. PSK prolonged significantly the life span of C3H/He mice bearing syngeneic plasmacytoma X5563 in a schedule- and dose-dependent manner. PSK was most effective when administered at 100 mg/kg every other day ten times starting from the day after tumor inoculation. The administration of PSK enhanced significantly the cytostatic activity of peritoneal exudate plastic-adherent cells and the cytolytic activity of spleen cells after in vitro incubation with mitomycin C-treated tumor cells. In addition, PSK restored the cytokine-producing capacity of spleen cells suppressed in tumor-bearing mice after in vitro incubation with mitogen. Sera from tumor-bearing mice suppressed the activity of such effector cells as well as the interleukin 2-producing capacity of spleen cells, but sera from PSK-treated tumor-bearing mice prevented this suppression. These results suggest that PSK enhances antitumor immunity by reducing immunosuppressive activity of serum from tumor-bearing mice.

Adjuvants, Immunologic↗

PubMed1990

Competitive action of a biological response modifier, PSK, on a humoral immunosuppressive factor produced in tumor-bearing hosts.

We investigated the effect of PSK, a protein-bound polysaccharide obtained from the basidiomycetes Coriolus versicolor, on an immunosuppressive factor produced in tumor-bearing animals. Oral administration of PSK suppressed the growth of the tumor in C3H/He mice bearing X5563 plasmacytoma or MH134 hepatoma, but affected mice bearing MM102 mammary tumor little. PSK prevented the reduction in splenic lymphocyte blastogenesis caused by phytohemagglutinin that occurs in mice bearing X5563 tumors or MH134 hepatoma. The lymphocyte blastogenesis affected little by tumor or PSK in mice bearing MM102 tumors. The effect of sera on the blastogenesis of lymphocytes caused by phytohemagglutinin was different with different tumors in the C3H/He mice. Serum of mice bearing X5563 tumors inhibited blastogenesis, but serum of mice bearing MH134 hepatoma or MM102 tumors promoted it. The sera of mice bearing MH134 hepatoma contained both inhibitory and promotive factors; those of mice bearing X5563 tumors contained an inhibitory factor, and those of mice bearing MM102 tumors contained a promotive factor. The oral administration of PSK reduced the inhibition caused by the sera of mice bearing X5563 tumors. The promotive activity of sera from mice bearing MH134 hepatoma was augmented by PSK; that of sera in mice bearing MM102 tumors was not affected by PSK. Living Bacillus Calmette-Guérin did not have such effects in any of these mice. Serum immunosuppressive activity was also reduced by PSK in various tumor lines of rodents. These results suggest that PSK acts by reducing the activity of immunosuppressive factors produced in tumor-bearing hosts.

Administration, Oral↗

PubMed1989

Treatment with Krestin combined with mitomycin C, and effect on immune response.

The combination effects of Krestin (PSK) and mitomycin C (MMC) were examined in experimental tumor models. PSK was administered either orally or intraperitoneally. Delayed-type footpad reaction and antibody formation against sheep erythrocytes were measured in hosts of which immune functions were depressed by tumor burden. Results of the experiment indicated that the simultaneous administration of PSK and MMC significantly increased the survival rate of tumor-bearing mice and restored more effectively their immune functions compared to those of nontreated tumor-bearing controls or tumor-bearing hosts treated with a single agent.

Animals↗

PubMed1989

Tumor growth-promoting effect of immunosuppressive substance in mice.

The effect of immunosuppressive (IS) substance obtained from cancerous ascitic fluid on tumor growth and host immunity in plasmacytoma X5563-bearing C3H/He mice is described. IS substance given in three injections, before and after tumor inoculation caused: (a) enhanced tumor growth, (b) marked reduction in survival times, (c) inhibition on Con-A response of spleen cells. Depressed natural killer (NK) activity was observed in normal and tumor-bearing mice treated with IS substance. The data presented here suggest that IS substance suppresses both humoral and cellular immunoresponsiveness and tumor cells evade immune surveillance or immunologically mediated removal.

Animals↗

PubMed1988

Production of antiserum against antitumor protein-bound polysaccharide preparation, PSK (Krestin) and its pharmacological application.

Antiserum against a protein-bound polysaccharide preparation (PSK) was produced by immunizing New Zealand White rabbits with PSK. The intestinal absorption of PSK in mice was visualized by indirect immunofluorescent staining with anti-PSK serum. The change in blood levels of 14C after oral administration of 14C-PSK and the recovery of 14C by antiserum were determined. The results indicated that antigenic epitopes in PSK are not completely destroyed during the process of digestion, absorption and distribution, but the changes of serum levels of 14C radioactivity differ from those of immunoreactive radioactivity. These results suggest that multiple processes are involved in the fate of PSK administered orally.

Administration, Oral↗

PubMed1988

Effect of PSK, a protein-bound polysaccharide from Coriolus versicolor, on drug-metabolizing enzymes in sarcoma-180 bearing and normal mice.

The effects of PSK and Propionibacterium acnes (anaerobic Corynebacterium) on hepatic drug-metabolizing enzymes were studied using sarcoma-180 bearing and non-tumor bearing mice. PSK had no influence on aminopyrine N-demethylase and aniline hydroxylase activities, cytochrome P-450 concentration in hepatic microsomes, and the reductase activity of cytochrome c in normal mice. The content of cytochrome P-450 was not significantly reduced in S-180 bearing mice. On the other hand, P. acnes administration significantly decreased the amount of cytochromes P-450 and b5 and aminopyrine N-demethylase activity. When FT-207 (Tegafur) was administered orally to S-180 bearing mice combined with the immunoadjuvants, only P. acnes significantly reduced the 5-FU levels in the serum and some organs.

Adjuvants, Immunologic↗

PubMed1988

Effects of PSK on resistance to bacterial infection in splenectomized mice.

Nontumor-bearing C3H/He mice were splenectomized and intravenously inoculated 7 days later with Streptococcus pneumoniae, Pseudomonas aeruginosa, or Escherichia coli. The survival rate was reduced by splenectomy in the animals inoculated with S. pneumoniae, but did not change in those inoculated with P. aeruginosa or E. coli. When splenectomy was performed 2 days after transplantation of X5563, and bacteria were inoculated 7 days after the operation, the survival rate was reduced even in those inoculated with P. aeruginosa or E. coli, and elimination of the bacteria from the blood and liver was delayed. This reduction in resistance to infection was alleviated by oral administration of PSK after the splenectomy.

Animals↗

PubMed1987

A biological response modifier, PSK, inhibits reverse transcriptase in vitro.

We found that PSK has an antiviral effect on human immunodeficiency virus (HIV) in vitro. One of the mechanisms of this effect is attributable to the inhibition of binding of HIV with lymphocytes. Here, we found that PSK inhibits reverse transcriptase in a non-competitive way in vitro. Such inhibition may be important in its anti-HIV effect as well as its inhibitory effect on the binding of HIV with lymphocytes.

Acquired Immunodeficiency Syndrome↗

PubMed1987

Influence of PSK (Krestin) on resistance to infection of Pseudomonas aeruginosa in tumor-bearing mice.

C3H/He mice were inoculated with Pseudomonas aeruginosa by various routes 1 day after X5563 transplantation or 4 days after cyclophosphamide (CY) administration. Administration of PSK (Krestin) i.p. or p.o. to the tumor-bearing mice or CY-treated tumor-bearing mice resulted in an increase in survival rates. Viable P. aeruginosa were inoculated i.v. on day 0 into mice inoculated with tumor cells on day -12 and vaccinated with killed P. aeruginosa on day -10, or into mice inoculated with tumor cells on day -15, treated with CY on day -14 and vaccinated on day -10. Resistance to infection, which is enhanced by vaccination, was depressed by tumor burden or treatment with CY, but such depression was prevented by PSK administration.

Adjuvants, Immunologic↗

PubMed1987

Determination of an immunosuppressive substance in serum by latex particle electrophoresis.

The level of immunosuppressive substance (IS), which increases in the serum of patients with cancer, was determined by an assay based on particle electrophoresis. Polystyrene latex particles (PLP) were coated with IS, which was extracted from the ascitic fluid of patients with cancer. The IS was a glycoprotein with a molecular weight of about 52,000, and an isoelectric point in the range pH 2.7-3.3. When the IS on the surface of the PLP reacted with the anti-IS antibody, the mean electrophoretic mobility of the PLP changed from -3.16 to +0.21 micron.s-1.V-1.cm in the medium of pH 7.2 and ionic strength I = 0.0154. After preincubation of anti-IS antiserum and tested serum, the PLP coated with IS were added to this solution. It was incubated again and then the surface charge of the PLP was measured by an automatic cell-electrophoretic instrument. This method was used to determine the IS concentration in the serum of cancer patients and pregnant women. When compared to healthy controls, the serum IS level was significantly higher in patients with cancer, and lower in pregnant women. The assay based on latex-particle electrophoresis proved to be a sensitive and rapid method for determining the IS level in serum.

Electrophoresis↗

PubMed1987

Tumor growth promoting activity of an immunosuppressive substance and its modulation by protein-bound polysaccharide PSK.

The role of an immunosuppressive substance (IS), which is increased in the serum of tumor-bearing animals, was examined in rats. IS isolated from cancerous ascites fluid of rats was administered to Walker 256 tumor-bearing rats to examine changes in the serum level of IS, tumor growth and survival rate. PSK, an immunomodulator, was also administered. Serum IS increased with tumor growth. The administration of IS to tumor-transplanted rats caused the tumor to grow and shortened the animals' survival time. The administration of PSK, however, inhibited the increase in serum level of IS, resulting in the suppression of tumor growth and a prolongation of survival time. The findings suggested that IS is a useful parameter for predicting not only tumor growth but also the therapeutic effect of immunomodulators such as PSK.

Adjuvants, Immunologic↗

PubMed1987

Purification and characterization of immunosuppressive (IS) substance obtained from ascitic fluids of patients with gastrointestinal cancer.

An immunosuppressive substance was isolated from ascitic fluids of patients with advanced colon cancer by means of ammonium sulphate precipitation and preparative isoelectric focusing. This was a glycoprotein with an isoelectric point of pH 2.7-3.3, a molecular weight of about 52,000, and a sedimentation coefficient of 4.0S. The substance showed a single band on ordinary disc electrophoresis, but it was separated into several bands by gel isoelectric focusing, due to the structural variety of the sugar moiety. The results of physicochemical analysis indicate that the amino acid composition of this glycoprotein was indistinguishable from that of alpha 1-acid glycoprotein (alpha 1-AG), but its molecular weight, its carbohydrate content, and composition were distinctly different. Furthermore, this glycoprotein was found to have higher immunosuppressive activity than that of alpha 1-AG in both the in vitro and in vivo assays. This glycoprotein, which we called "IS substance," is a cancer-related substance synthesized in cancer patients.

Amino Acids↗

PubMed1987

Restoration of immune responsiveness by a biological response modifier, PSK, in aged mice bearing syngeneic transplantable tumor.

PSK (Krestin) is a protein-bound polysaccharide isolated from cultured mycelia of Coriolus versicolor in basidiomycetes. PSK is a biological response modifier which possesses unique characteristics. We investigated the effects of PSK on the immune response of aged C57BL/6 mice bearing a syngeneic transplantable tumor adenocarcinoma 755. (a) In C57BL/6 mice, the delayed foot pad reaction against sheep erythrocytes and resistance to syngeneic tumor challenge reached a peak when the mice were at 30 weeks of age, and decreased at 50-60 weeks of age. The serum of normal mice exerts a modifying effect on blastogenesis of lymphocytes to phytohemagglutinin. The positive effect reached a peak at 30 weeks of age, and thereafter declined with age. (b) When adenocarcinoma 755 was inoculated to C57BL/6 mice at 10-, 30- and 60-weeks of age, immune responses were depressed in 10-week-old and 60-week-old mice. PSK prevented such depression. However, in 30-week-old mice, tumor-induced suppression was slight, and administration of PSK to them increased proportion of mice which did not develop a tumor. (c) In 60-week-old tumor-bearing mice, the antitumor effects was increased with a combination of PSK and adoptive transfer of spleen cells from 10-week-old normal mice. The immune responses of mice, which change with the progress of age, are depressed by tumor burden. The administration of PSK to aged mice is effective to restore immune responses from tumor-induced suppression.

Adenocarcinoma↗

PubMed1987

Involution of the thymus in tumor-bearing mice and its restoration by PSK. II. Mechanism of the involution and its restoration.

In C3H/He mice, the weight and cell number of the thymus were reduced and the size distribution (scatter profile measured by flow cytometer) of the thymus cells was changed 1 week after subcutaneous inoculation of X5563 plasmacytoma. This involution and change were prevented by intraperitoneal or oral administration of PSK. We examined the mechanism of this involution and change in thymus and the effect of PSK on them. In X5563-bearing C3H/He mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only per organ but also per 1 mg of thymus tissue. Such reduction was inhibited by PSK. The substance (IS substance) which possessed a suppressive activity against mitogen induced lymphocyte proliferation, was partially purified from the ascites of X5563-bearing mice by the combination of ammonium sulfate precipitation and Sephacryl S-200 chromatography. IS substance was demonstrated to suppress the antibody response and delayed type foot-pad response against sheep red blood cells in mice. The reduction of weight and cell number and the change of scatter profile in thymus were caused by injection of this substance even in tumor-free mice. The restorative effects of PSK were observed also in IS substance injected mice. These results suggested that the various changes in the thymus observed in tumor-bearing mice might be attributable to the suppression of cell proliferation in the thymus, that such suppression was caused at least partly by an immunosuppressive substance which possessed inhibitory activity against lymphocyte proliferation, and that PSK had an antagonistic activity against such a substance so as to restore the function of the thymus in tumor-bearing hosts.

Animals↗

PubMed1987

Changes in electrophoretic mobility pattern of erythrocytes in patients with paroxysmal nocturnal hemoglobinuria.

The electric surface charge of erythrocytes in patients with paroxysmal nocturnal hemoglobinuria (PNH) was analyzed by means of a fully automated cell electrophoretic instrument (Parmoquant-L). The electrophoretic mobility of PNH erythrocytes decreased significantly and showed a broader pattern. After a blood transfusion, erythrocytes of PNH patients showed a bimodal pattern because of the emergence of the higher mobility peak corresponding to normal erythrocytes. However, the next day after transfusion, this new peak disappeared. Furthermore, the next day after administration of Prednisolone, the main peak of the mobility pattern shifted to the higher side, and after treatment for 7 days, the pattern showed several peaks and tended to disperse. Reticulocytes had higher complement lysis sensitivity, lower cholinesterase activity and lower electric surface charge, and it was shown that PNH erythrocytes consisted of 2 populations. Studies on the electrophoretic mobility patterns of PNH erythrocytes under various conditions can be useful in understanding the properties of erythrocyte membrane surfaces.

Blood Transfusion↗

PubMed1987

Effects of PSK, an antitumor protein-bound polysaccharide, on the surface charge of lymphocytes in X5563-bearing mice.

Spleen and thymus cells from X5563 plasmacytoma-bearing mice treated with PSK (krestin) were analyzed by cell electrophoresis and flow microcytometry. A splenocyte electrophoretic pattern showed that an intermediate mobility peak (IMC), which appeared between the low (B cells) and high (T cells) peaks as the tumor developed, was depressed by the administration of PSK. Thy-1+ cells and asialo-GM1+ (aGM1+) cells decreased with tumor growth, and null cells without a marker of Ig, Thy-1 nor aGM1 increased. However, these changes were corrected by the administration of PSK. As the tumor grew, a thymocyte electrophoretic pattern showed that the incidence of low mobility cells, corresponding to immature cells, decreased, and that of high mobility cells, corresponding to mature cells in the medullary zone, increased. However, PSK suppressed the changes. The tumor did not disappear but life span was prolonged (121%) by the administration of PSK. These results lead to the conclusion that the administration of PSK prevented the changes in surface charge and markers of lymphocytes due to tumor burden, and restored the immunological responsiveness even in the syngeneic system.

Adjuvants, Immunologic↗

PubMed1986

Evaluation of anticancer drugs by lymphocyte electrophoresis.

The spleen cells in tumor-bearing and normal mice treated with Krestin (PSK), mitomycin C (MMC) or adriamycin (ADM) were analyzed by cell electrophoresis and flow microcytometry. In normal mice, the splenocyte electrophoretic mobility histogram was observed as a bimodal pattern, and low and high mobility cells (LMC and HMC) corresponded with B and T cells, respectively. In sarcoma-180-bearing mice, an intermediate mobility peak (IMC) appeared between the low and high peaks. Although every anticancer drug depressed the IMC when the tumor was cured, MMC reduced the absolute number of splenic Ig+ and Thy-1+ cells, and ADM injured Ig+ cells in normal as well as in tumor-bearing mice. PSK, however, depressed splenomegaly by tumor-burden in spite of a slight increase in splenocytes of normal mice. In a previous paper, it was reported that the thymocyte mobility histogram was restored to a normal pattern by treatment with PSK in tumor-bearers, while it was made more abnormal by treatment with MMC because of injury to cortical thymocytes. From these results, it may be considered that an anticancer drug which restored the splenocyte mobility histogram to a normal pattern without damages to thymocytes is preferable for cancer therapy.

Animals↗