Biomedical subjects

C Yoshikumi

Publications and source records attributed to C Yoshikumi.

At least 37 records · Page 2Linked to original sources

PubMed1986

[Effects of krestin (PSK) on drug-metabolizing enzymes with special reference to the activation of FT-207].

The effects of PSK on hepatic drug-metabolizing enzymes were investigated using Sarcoma 180-bearing and non-tumor-bearing ICR mice. PSK, an immunomodulator, has been commonly used in combination with tegafur for post-operative adjuvant chemotherapy. Tegafur is a typical masked compound transformed into 5-FU by the hepatic drug-metabolizing enzyme P-450. It has been reported that immunostimulants such as BCG and anaerobic Corynebacterium suppress the drug metabolism. PSK and Propionibacterium acnes were administered to mice inoculated s.c. with Sarcoma 180. It was demonstrated that Propionibacterium acnes had an effect of inhibiting these enzymatic activities, especially the amount of P-450 and cytochrome b5 and aminopyrine demethylation. On the other hand, PSK had no influence on the drug-metabolizing enzymes. Propionibacterium acnes was shown to decrease the 5-FU level in organs and sera of mice given FT-207 orally. By contrast, PSK showed no difference in 5-FU level compared to controls, indicating that PSK had no inhibitory effect on the activation of FT-207 by hepatic drug-metabolizing enzymes.

Aminopyrine↗

PubMed1986

[Involution of the thymus in tumor-bearing mice and its restoration by PSK (2)].

We examined the effect of PSK on involution of the thymus in tumor-bearing mice. The weight and cell number of the thymus decreased and the size distribution (scatter profile) of thymus cells was changed in X5563-bearing C3H/He mice. Also in these mice, 3H-thymidine incorporation into the thymus was reduced compared with that in control mice, as evaluated not only by per organ but also by per 1 mg of thymus tissue. Such an involution was also observed in tumor-free mice injected with immunosuppressive substance, which had been obtained from ascites of X5563-bearing mice and revealed suppressive activity against lymphocyte proliferation. PSK administration prevented such modulation in the thymus of tumor-bearing mice and immunosuppressive substance-injected tumor-free mice. In other words, it is considered that the various changes in the thymus demonstrated in tumor-bearing mice may be attributable to the suppression of cell proliferation in the thymus, that such suppression is caused at least partly by an immunosuppressive substance which possesses inhibitory activity against lymphocyte proliferation, and that PSK has an antagonistic activity against such a substance so as to restore the function of the thymus in tumor-bearing hosts.

Animals↗

PubMed1986

[Restoration of depressed immune responses by PSK in C3H/He mice bearing the syngeneic X5563 tumor].

PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The effects of PSK on immunologic responsiveness were investigated in C3H/He mice bearing syngeneic X5563 tumor. The results were as follows. elayed foot pad reaction and antibody-forming capacity to sheep erythrocytes were depressed in tumor bearing mice, and such depression was prevented by oral or intraperitoneal administration of PSK. In vitro cytotoxic activity of splenic lymphocytes against the tumor was augmented by PSK administration. Antitumor effect was augmented by combination of PSK and X-irradiation. Delayed foot pad reaction to sheep erythrocytes was suppressed in normal C3H/He mice given immunosuppressive substance obtained from tumor-bearing mice, and the depressed reaction recovered to the normal level following PSK administration. These results show that PSK is effective in the syngeneic murine tumor system.

Adjuvants, Immunologic↗

PubMed1986

[Competitive effect of PSK against the immunosuppressive effect induced in the sera of mice bearing syngeneic tumors].

PSK is a protein-bound polysaccharide prepared from cultured mycelium of Coriolus versicolor. The appearance of an immunosuppressive effect in sera of tumor-bearing mice and its elimination by oral administration of PSK were investigated using an in vitro assay of blastoid transformation of normal spleen cells in response to PHA. (1) An inhibitory effect appeared in sera of X5563 plasmacytoma-bearing mice, while a facilitating effect was noted in sera of MH134 hepatoma- and MM 102 mammary tumor-bearing mice. (2) The presence of both an inhibitory and a facilitating factor was shown by Sephacryl gel fractionation. (3) Oral administration of PSK resulted in the elimination of the inhibitory effect from sera of X5563-bearing mice. The facilitating effect of sera from MH134-bearing mice was augmented by PSK administration, but that in sera from MM102-bearing mice was not influenced by such treatment. The summarized effects of these factors may be expressed as various types of effects in serum and PSK may be effective in the elimination of a suppressive factor from such sera.

Adjuvants, Immunologic↗

PubMed1986

[Restoration of immunologic responsiveness by PSK in tumor-bearing animals].

PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.

Adjuvants, Immunologic↗

PubMed1985

Cloning of sequences induced and suppressed by administration of PSK, antitumor protein-bound polysaccharide.

To elucidate the effects of PSK, a protein-bound polysaccharide from Coriolus versicolor, on gene expression in tumor cells, we prepared cDNA clone libraries from PSK-treated and untreated cells of a rat ascites hepatoma line, AH66, which was previously shown to be susceptible to the antitumor action of this compound. Two PSK-induced and one suppressed cDNA clones were selected from these libraries by using a differential colony hybridization and RNA blot hybridization. PSK was thus shown to have a direct effect on the transcription and consequently on the translation of tumor cells.

Animals↗

PubMed1984

[Effect of PSK on the recovery of macrophage function in tumor-bearing mice].

Chemotactic response of macrophage to PHA was depressed at early stages in allogeneic sarcoma 180-bearing ICR mice and syngeneic X5563-bearing C3H/He mice and their depressed response were restored to the normal levels by PSK. Macrophages-dependent resistance against Listeria monocytogenes at early phase of infection was depressed at the early stage after tumor inoculation. The depressed resistance was restored by PSK in X5563-bearing mice and by a combination of tumor resection and PSK in sarcoma 180-bearing mice.

Animals↗

PubMed1983

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

In Balb/C mice, the size and weight of the thymus and the number of thymus cells were reduced 1 week after the subcutaneous inoculation of Meth A fibrosarcoma. These changes were prevented by the intraperitoneal administration of PSK. In normal mice, the majority of thymus cells are large and the minority are small as demonstrated by analysis with a fluorescence activated cell sorter. In tumor-bearing mice, the number of large cells are decreased and the number of small cells are relatively increased. PSK prevented such a modulation in tumor-bearing mice.

Animals↗

PubMed1975

Restoration of antibody-forming capacities by PS-K in tumor-bearing mice.

PS-K, a protein-bound polysaccharide from a basidiomycetes, was found to suppress tumor growth after grafting of sarcoma-180 or Ehrlich tumor in ICR mice. In the present study, effect of PS-K on antibody-forming capacities was examined in tumor-bearing mice and normal controls. 1) PS-K did not enhance the capacities of normal mice to produce antibodies against sheep erythrocytes (SRBC), hamster erythrocytes (HRBC), and trinitrophenyl group (TNP). 2) The capacities of mice to produce IgG antibody against SRBC, IgM antibody aganist HRBC, and IgG antibody against TNP were depressed after grafting of sarcoma-180. Intraperitoneal injection of PS-K restored these capacities to the normal levels. 3) Oral as well as intraperitoneal administration of PS-K restored the capacity of the mice bearing sarcoma-180 to produce IgG antibody against SRBC. 4) The capacity to produce IgG antibody against SRBC was depressed after grafting of Ehrlick tumor and it recovered to the normal level after intraperitoneal injection of PS-K. These results showed that antibody-fforming capacity of mice was depressed after tumor grafing and recovered after administration of PS-K.

Animals↗

PubMed1975

Mouse strain difference in the expression of antitumor activity of PS-K.

Effect of PS-K on tumor growth and antibody production was studied in inbred C57BL/6, SL, C3H/He, and AKR mice, and in colony-bred ICR mice. (1) PS-K exhibited antitumor activity on sarcoma-180 in ICR mice, but not in AKR mice. Growth of sarcoma-180 was suppressed to the intermediate extent in other strains. (2) In ICR strain, antibody production against trinitrophenyl was depressed in mice bearing sarcoma-180 and restored by PS-K. In AKR mice, on the other hand, antibody production was not depressed in tumor-bearing state and was not augmented by PS-K. Other strains showed intermediate degrees of suppression of antibody-producing capacity by sarcoma-180 and its restoration by PS-K.CR strain, the growth of Ehrlich tumor as the challenge tumor was enhanced in mice bearing sarcoma-180 as compared to that in controls. After the treatment with PS-K in this strain, however, not only the growth of sarcoma-180 but also of Ehrlich tumor was inhibited completely. On the other hand, the growth of Ehrlich tumor in AKR strain was neither enhanced in mice bearing sarcoma-180 nor inhibited by PS-K.

Animals↗

PubMedDate not supplied

Effects of the protein-bound polysaccharide preparation, PSK on spontaneous breast cancer in mice.

The protein-bound polysaccharide preparation, PSK was tested for its ability to suppress carcinogenesis in spontaneous tumours in C3H/OuJ mice. They were divided into two groups of 40 individuals each. A normal diet was given to one group, establishing a control population, while the other group had 2% PSK added to their feed. Amount of feed consumed, body weight and tumour size were recorded weekly for 1 year. Within 15 weeks, 90% of the control population had developed tumours. In the test group the incidence of cancer and the number of tumours was significantly suppressed, and survival rates were improved. The amount of feed consumed and body weights of control and test groups were about the same.

Administration, Oral↗

PubMedDate not supplied

Antitumor effects of 3-[p-(N,N-bis-(2'-chloroethyl)amino)-phenyl]-L- alanine conjugated with human immunoglobulin (K18).

K18 (3-[p-(N,N-bis(2'-chloroethyl)amino)- phenyl]-L-alanine conjugated with human immunoglobulin) is a newly developed antitumor agent. LD50 values of K18 in animals were quite high, suggesting its low acute toxicity. This drug showed anti-tumorigenicity not only on an experimental animal tumor (Walker 256), but also on a human tumor transplantable into nude mice (RCC-13). A distribution study clarified the unique properties of K18 to accumulate and remain in the tumor site with a high rate.

Animals↗

PubMedDate not supplied

Effect of PSK on the serum level of immunosuppressive substance in splenectomized rats.

Tumor-bearing rats with and without splenectomy were used for an immunological study on the effects of PSK, an immunomodulator, with respect to the survival rate and serum level of immunosuppressive (IS) substance. There was no significant difference in survival rates between the tumor-resected and tumor-resected-plus-splenectomy groups. The IS substance level in the former group was higher than that in the latter group. Normalization of IS substance level and prolongation of survival were observed in the group administered PSK. PSK can be effective in combination with surgical treatment.

Animals↗

PubMedDate not supplied

In vivo antineoplastic activity of mouse or human IgG conjugated with melphalan.

IgG of normal female ICR mice was obtained and covalently conjugated with an alkylating agent, melphalan. The conjugate exhibited marked antitumor activities against Sarcoma 180 and Erhlich carcinoma cells inoculated subcutaneously into ICR mice. Based upon this experiment, melphalan was conjugated with human IgG. Antitumor activities of the conjugate, named K18, were tested against a variety of murine tumor cell lines in vivo. Additionally, K18 was tested in vivo against MX-1, MK-2 and LC-10 human tumor cell lines (of the breast, stomach, and lung respectively). The results showed antineoplastic activities on both murine and human tumor cell lines, thus indicating a possible new antitumor agent.

Animals↗

PubMedDate not supplied

Tumor and tissue distribution of 125I-labeled natural and antitumor antibodies in murine experimental tumor systems.

The binding and tissue distribution of 125I-labeled rabbit anti-sarcoma 180 (S-180) immunoglobulin G (IgG) (RAS-180G), normal rabbit IgG (NRG) and ICR mouse IgGs from normal (NMG) and S-180-bearing ICR mice (AS-180G) were studied in ICR mice bearing S-180. 125I-labelled IgGs preparted from normal (NC57G) or Adenocarconoma 755 (Ca 755)-bearing C57BL/6 mice (A755G) were also examined in C57BL/6 mice bearing ca755. Not only RAS-180G and AS-180G but also NRG and NMG persisted in the tumor site. This result suggests that allogeneic natural IgG could be used as a carrier protein for antitumor agents.

Adenocarcinoma↗

PubMedDate not supplied

Comparative study of alpha 1-acid glycoprotein molecular variants in ascitic fluid of cancer and non-cancer patients.

alpha 1-Acid glycoproteins (alpha 1-AG) were collected from the ascites of patients with liver cirrhosis or liver cancer, respectively, and their physical, chemical, and biological properties were compared. The substance obtained from patients with liver cancer showed a 2-3 times higher inhibitory effect on [3H]thymidine uptake by human peripheral lymphocytes stimulated with PHA than that obtained from patients with cirrhosis. The two substances showed differences in their affinity to wheat germ agglutinin (WGA) and concanavalin A (Con A). Of the fractions obtained by lectin affinity chromatography, the Con-A bound fraction showed the greatest lymphocyte proliferation inhibitory activity. The alpha 1-AG levels were elevated in both the patients with cancer and those with infectious disease, but the level of the Con-A bound fraction was elevated only in those with cancer. This study suggests that the molecular variants of alpha 1-AG differ in their carbohydrate structure with the disease, and that the cellular immunity of the host way be partially controlled by changes in the content of these molecular variants.

Ascitic Fluid↗

PubMedDate not supplied

Effect of PSK on cytotoxicity against sarcoma-180 in tumor-bearing mice.

The effect of PSK, a protein-bound polysaccharide with antitumor activity, on the host defence mechanism against tumor in sarcoma-180-bearing mice was examined. PSK restored the capacity to generate cytotoxic lymphocytes and complement-requiring cytotoxic antibody in tumor-bearing mice. PSK did not, however augment cytotoxic activity in tumor-free mice.

Adjuvants, Immunologic↗

PubMedDate not supplied

The effect of a biological response modifier, PSK, on the intestinal immune system in tumor-bearing mice.

We have previously shown that oral administration of PSK not only exerts antitumor activity, but also restores immune response in tumor-bearing mice. In order to analyze the immunomodulative effect of PSK, we investigated the effects of oral PSK on the intestinal immune systems in ICR mice bearing sarcoma 180. Oral administration of PSK increased the number of Peyer's patches that developed relatively well, and led to recovered mitogenic response of lymphocytes from gut-associated lymphatic tissue and responsiveness to oral preimmunization with SRBC in tumor-bearing mice. These results suggest that PSK modulates the immunity in intestinal tract of tumor-bearing mice.

Adjuvants, Immunologic↗