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At least 19 recordsLinked to original sources
PubMed1993

Inhibitory effects of sizofiran on anticancer agent- or X-ray-induced sister chromatid exchanges and mitotic block in murine bone marrow cells.

The inhibitory effects of a biological response modifier (BRM), sizofiran, on sister chromatid exchanges (SCEs) in the bone marrow cells of mice treated with various anticancer agents or irradiation were investigated. Sizofiran (10 mg/kg i.m.) inhibited SCEs induced by mitomycin C (2 mg/kg i.v.), adriamycin (20 mg/kg i.v.) and cyclophosphamide (20 mg/kg i.v.) by about 20%, respectively. Analysis of the SCEs in vivo after irradiation plus sizofiran indicated that SCE levels were significantly lower than those observed in mice exposed to irradiation without sizofiran. Moreover, the effects of sizofiran were dependent on the timing of administration. Our results indicated that sizofiran should be administered simultaneously or soon after irradiation in order to minimize damage. Sizofiran also markedly restored the bone marrow cell mitosis which had been suppressed by anticancer agents, and this action was closely correlated with the prevention of increase in SCEs. These results indicate that in addition to immunopotentiating activity, sizofiran may play a role in preventing chromosomal damage induced by cancer chemotherapy and radiotherapy.

Animals↗
PubMed1995

Activated (HLA-DR+) T-lymphocyte subsets in cervical carcinoma and effects of radiotherapy and immunotherapy with sizofiran on cell-mediated immunity and survival.

A prospective randomized trial on 312 patients with locally advanced cervical carcinoma (FIGO stages IB-IV) was carried out. The 5-year survival in 90 patients treated with radiotherapy and antitumor polysaccharide sizofiran, an extract from the culture broth of Schizophyllum commune Fries, in combination was significantly (P = 0.045) better than that in 82 patients treated with radiotherapy alone. Treatment with sizofiran and 5-fluorouracil in combination improved (P = 0.003) the 5-year survival in 60 patients treated with radiotherapy. In 244 cervical carcinoma patients, the percentage of activated CD8+ (CD8+HLA-DR+) T cells in the CD8+ T-cell subsets in peripheral lymphocytes increased significantly as the disease progressed. A similar tendency was observed in the percentage of activated CD4+ (CD4+HLA-DR+) T cells in the CD4+ T-cell subsets. These immunologic parameters were significantly increased by radiotherapy, but not by surgery. Sizofiran accelerated a recovery in the activated CD8+ T cells in the CD8+ T-cell subsets compared with that of sizofiran nontreated patients after radiotherapy. Our data show that possible immune impairment in cervical carcinoma may be caused by disturbances in cell-mediated immunity, and that sizofiran is an effective immunotherapeutic agent for cervical carcinoma because it stimulates a rapid recovery of the immunologic parameters impaired by radiotherapy.

CD4-CD8 Ratio↗
PubMed1992

Augmenting effect of sizofiran on the immunofunction of regional lymph nodes in cervical cancer.

The immunomodulating effect of sizofiran on regional lymph nodes (RLN) was studied in cervical cancer and benign gynecologic tumors comparatively between treated patients (sizofiran intramuscularly (1) 1 day (20 mg) before and (2) 8 days (20 mg) and 1 day (20 mg) before surgery; n = 34) and untreated patients (n = 21). The RLN (internal iliac lymph nodes) were dissected surgically, and freshly obtained mononuclear (MN) cells were studied to observe interleukin-2 (IL-2) production and lymphokine-activated killer cell and natural-killer cell activities. The infiltration of surface phenotype of MN cells into RLN was determined semiquantitatively by immunohistochemistry. Sizofiran augmented IL-2 production of RLN, which was accompanied by a marked increase in the number of cells stained with anti-Leu-3a and IL-2 receptor. This effect was found more often in Stage Ib disease than in Stage 0, and it was not observed in benign tumors. These results suggest that stimulation with some antigens (e.g., cancer antigen in the current study) is necessary to induce immunoaugmentation by sizofiran which has no antigenicity. The augmenting effect was seen even in lymph nodes involved by advanced cervical cancer. Therefore, sizofiran was found to be a potent biologic response modifier in patients with cervical cancer.

Adjuvants, Immunologic↗
PubMed1991

Effect of a glucan, sizofiran, on natural-killer activity of 5-fluorouracil-treated murine bone marrow cells.

The number of bone marrow cells in C3H/He mice was reduced 3-4 days after treatment with 130 mg/kg intraperitoneal 5-fluorouracil (5-FU). Higher rates of spontaneous proliferation and natural killer (NK) activity, accompanied by an increase in asialoGM1-positive cells, were observed in treated mice. When sizofiran at a dose of 200 micrograms/animal was intramuscularly injected after 5-FU treatment, the rates of proliferation and NK activity of bone marrow cells were higher than with 5-FU alone. The cell number was not influenced by sizofiran alone. These results indicate that all precursors of the various mature cell types (including NK cells) differentiate and regenerate rapidly to replace cells damaged by 5-FU treatment, and that sizofiran has the potential to assist this recovery. These results suggest that administration of sizofiran after chemotherapy may be useful in cancer patients.

Animals↗
PubMed1991

Clinical outcome of postoperative adjuvant immunochemotherapy with sizofiran for patients with resectable gastric cancer: a randomised controlled study.

Adjuvant immunochemotherapy using the antitumour polysaccharide sizofiran (SPG), an extract from the culture broth of Schizophyllum commune Fries, was prescribed randomly for 386 Japanese patients with resectable gastric cancer. Although the overall survival probability for 5 years did not differ between the SPG and control groups, in 264 patients with curatively resected cancer, the probability to 5 year survival and to recurrence in the sizofiran-administered patients was better than in the controls. In the multivariate analysis, four of six prognostic factors correlated with the prognosis of the 264 patients who underwent curative surgery, that is, nodal involvement (chi 2 = 21.426, P = less than 0.0001), age distribution (chi 2 = 9.262, P = 0.010), sizofiran administration (chi 2 = 6.507, P = 0.011), and primary tumour size (chi 2 = 9.345, P = 0.025). Thus, patients with a curatively resected gastric cancer had a better prognosis when sizofiran was prescribed in combination with antitumour drugs.

Adjuvants, Immunologic↗
PubMed1993

Acceleration of natural killer (NK) cell recovery by a glucan, sizofiran, in anti-asialoGM1 antibody-treated mice.

The proportion of asialoGM1 positive cells and NK activity of murine splenic cells was reduced to almost zero one day after intravenous injection of rabbit anti-asialoGM1 antibody. The cells and the activity started to increase at the latest 3 days after the injection, although the proportion was far below that of the normal control. The proportion of asialoGM1 positive cells and NK activity increased more remarkably when 1,3-beta glucan, sizofiran, was administered intramuscularly one day after the antibody injection. The increases were dose related (50-1000 micrograms/mouse). The fact that sizofiran hastened the recoveries of splenic NK activity and asialoGM1 positive cells suggests sizofiran may have the activity to accelerate the differentiation of asialoGM1 positive NK cells.

Animals↗
PubMed2002

Graves' disease development during sizofiran treatment.

It has been reported that various types of immunoactivators can induce Graves' disease. We describe here a case of Graves' disease during treatment with sizofiran, an immunoactivator. A 42-year-old woman who had previously been in an euthyroid state with Hashimoto's thyroiditis, experienced thyrotoxicosis during continuous administration of sizofiran as immunotherapy for endometrial carcinoma. Since the TSH receptor-antibody was positive, and a thyroid scintigram showed diffuse goiter and high uptake, she was diagnosed as having Graves' disease. It is suggested that the administration of sizofiran may be one of the triggers of Graves' disease.

Adult↗
PubMed1993

Activation of peritoneal macrophages in patients with gynecological malignancies by sizofiran and recombinant interferon-gamma.

We investigated the influence of the combined use of sizofiran, a beta-1,3-glucan and a recombinant interferon-gamma (rIFN-gamma) upon biological activities of peritoneal macrophages (M phi). The number of peritoneal M phi and the production of cytokines (interleukin-1 beta, interferon-gamma and tumor necrosis factor) was increased by the combined treatment. Fully activated peritoneal M phi based on the increased number of elongated pseudopods were observed by electromicroscope. Sizofiran seems to assure a sufficient supply of M phi to kill tumor cells in the peritoneal cavity and co-administered rIFN-gamma seems to directly stimulate the accumulated M phi in addition to its direct cytotoxicity against tumor cells. This combination therapy may be a step to the prevention of the recurrence of gynecological malignancies including ovarian cancer, after a negative second-look laparotomy.

Adult↗
PubMed1992

Maintenance of the activation of peritoneal macrophages in patients with ovarian cancer by sizofiran and recombinant interferon-gamma.

Four patients with ovarian cancer received 20 mg of sizofiran, a beta-1,3-glucan (molecular weight: 450,000), intramuscularly one day before and 4, 7, 11, 14, 18 and 21 days after second look laparotomy and recombinant interferon-gamma (rIFN-gamma) intraperitoneally on the day of second look laparotomy and 4, 7, 11, 14, 18 and 21 days thereafter. The peritoneal cavity was washed with physiological saline and peritoneal macrophages (M phi) were isolated. The number of M phi increased 30-1600 times during the treatment period. The concentrations of interleukin-1, interferon-gamma, tumor necrosis factor and prostaglandin E2 were also found increased in the supernatant fluid of M phi cultured for 24 hours with 10 micrograms/ml of lipopolysaccharide. The present study demonstrated that the activation of peritoneal M phi could be maintained and its number was increased by repeated dosing of sizofiran and rIFN-gamma in combination every three or four days in patients with ovarian cancer. Peritoneal M phi thus activated may exert an antitumor effect on ovarian cancer.

Adult↗
PubMed1991

Effect of sizofiran, a polysaccharide, on interferon gamma, antibody production and lymphocyte proliferation specific for hepatitis B virus antigen in patients with chronic hepatitis B.

To examine whether sizofiran (SPG), a polysaccharide isolated from Schizophyllum commune Fries, could modulate the immune response of immunocompetent cells to hepatitis B virus (HBV) nucleocapsid antigens, we investigated in vitro the production of interferon-gamma (IFN-gamma) and antibody (antibody to HB core and e antigens; anti-HBc and anti-HBe), and proliferation by peripheral blood mononuclear cells (PBMC) from six patients with chronic hepatitis B and four control individuals in the presence of recombinant HBcAg and purified HBeAg. Sizofiran alone in culture and in combination with HBV Ag was found to enhance IFN-gamma production and the proliferative response of PBMC from the patients compared with corresponding medium or HBV Ag alone culture. In contrast, antibody production was not elicited by SPG alone, but amplified by the drug in HBcAg-stimulated culture. In vitro leukocyte IFN-alpha addition increased IFN-gamma production, but suppressed the proliferation of PBMC from both controls and patients in the presence or absence of SPG and HBV Ag. These results indicate that SPG is able to modulate both cellular and humoral immune responses specific for nucleocapsid antigens in patients with chronic hepatitis B.

Hepatitis B↗
PubMed1991

[Maintenance of the activation of peritoneal macrophage in patients with ovarian cancer by the repeated administration of sizofiran and interferon gamma].

Four patients with ovarian cancer were treated with a 20mg injection of sizofiran, a MW 450,000 beta-1,3-glucan, intramuscularly one day before and 4,7,11,14,18 and 21 days after second look laparotomy and with the administration of 2 million units of interferon gamma intraperitoneally at 0,4,7,11,14,18 and 21 days after second look laparotomy. Peritoneal macrophages were obtained from the patients by peritoneal washing with saline through an indwelled tube. The number of macrophages was increased to about 30 times after the treatment. The concentrations of interleukin 1, interferon gamma, tumor necrosis factor and prostaglandin E2 in the media of 24-hour cultured macrophage with 10 micrograms/ml of LPS were also increased throughout the treatment. These data suggest that the every 3 to 4 day treatment with sizofiran and interferon gamma maintained the activation of peritoneal macrophages which might lead to retention of the antitumor activity in patients with ovarian cancer.

Adult↗
PubMed1996

Intratumoral administration of sizofiran activates Langerhans cell and T-cell infiltration in cervical cancer.

In order to ascertain a correlation between infiltration of Langerhans cells (LCs) or T-cells in tumor tissues and the intratumoral administration of a biological response modifier, Sizofiran (SPG) was analyzed in cancer of the uterine cervix. Cancer specimens of 45 patients with stage II-III invasive cervical cancers were analyzed. SPG was administered to the cervical tumor at high and low concentrations (Strong SPG and weak SPG) as well as by intramuscular injection twice a week. LC and T-cell infiltrations to tumor tissues of the uterine cervix were studied immunohistochemically and electron microscopically. Of 10 patients with systemic but no local immunization, 1 (10.0%) showed an increase in LC infiltration and 2 (20.0%) showed a decrease. Of 15 patients with strong SPG immunization, 2 (13%) showed an increase and 5 (33%) showed a decrease. In contrast, of 20 patients with weak SPG immunization, the incidence of increase in LC infiltration was 55% (11 patients), significantly greater than the above-mentioned groups and none showed a decrease. Of the 20 patients with weak SPG administration, 3 (15%) showed T-cell infiltration before SPG administration, and 12 (60%) showed an increase in T-cell infiltration after SPG was given. Up on electron microscopy, Birbeck granules in the cytoplasm of LC significantly increased after SPG immunization, indicating activation of LC. In conclusion, the present study suggested that the LC and T-cell infiltrations in cancer tissues were augmented by intratumoral SPG administration at a certain concentration. Intratumoral administration of SPG may be applied to improve the prognosis after multidisciplinary treatment of advanced cervical cancer.

Adjuvants, Immunologic↗
PubMed1993

Improvement of long-term prognosis in patients with ovarian cancers by adjuvant sizofiran immunotherapy: a prospective randomized controlled study.

The effect of immunotherapy using sizofiran (SPG) on the prognosis of patients with ovarian cancers was prospectively studied in a total of 68 patients, who were randomly assigned to either a cisplatin, adriamycin and cyclophosphamide (PAC) therapy group or a PAC plus SPG combination therapy group. The survival rate was significantly higher in patients with stage Ic, II or III cancers treated with the PAC plus SPG combination, compared with the patients treated with PAC alone. In the SPG-receiving patients with stage Ic or more advanced cancers who were treated with four cycles or more of PAC, the outcome was improved (Cox-Mantel, p = 0.074; generalized Kruskal-Wallis, p = 0.032). Similar improvement was also observed in the patients with non-serous adenocarcinomas (Cox-Mantel, p-0.076; generalized Kruskal-Wallis, p = 0.045). No side effects attributable to SPG were recorded. The present results suggest that the use of SPG in combination with long-term chemotherapy improves the postoperative prognosis in ovarian cancer patients.

Adjuvants, Immunologic↗
PubMed1989

Clinical evaluation of sizofiran combined with irradiation in patients with cervical cancer. A randomized controlled study; a five-year survival rate.

Following a previous report we ascertained the effectiveness of sizofiran (Schizophyllan:SPG) to prolong the survival and time to recurrence of the patients with Stage II or III cervical cancer, as evaluated in a 5-year randomized controlled study conducted in 19 institutions in Japan. Of the overall patients with Stage II or III cancer, time to recurrence and survival rate in the group on SPG were significantly longer than in the control group. In the Stage II patients, there was significant difference in time to recurrence, and survival of SPG group tended to be longer than that of the control group. However, in the Stage III patients, there was no significant difference in either time to recurrence or survival rate.

Antineoplastic Agents↗
PubMed1992

Combination therapy of radiation and Sizofiran (SPG) on the tumor growth and metastasis on squamous-cell carcinoma NR-S1 in syngeneic C3H/He mice.

The efficacy of Sizofiran(SPG), a highly purified beta-1,3-D-glucan from the culture broth of basidiomycetes Schizophyllum commune Fries, in combination with local irradiation was investigated using squamous-cell carcinoma NR-S1 and syngeneic hosts of C3H/He mice. NR-S1 tumor was implanted sc in the thigh of C3H/He mice. When tumor grew to 4 mm in diameter, the local irradiation of 55 Gy was delivered. SPG was injected im at a dose of 5 mg/kg. When SPG was administered after irradiation, remarkable inhibition of tumor growth was observed in comparison with the radiation alone group. Furthermore, the combination effect of radiation and active immunotherapy using mitomycin C-treated NR-S1 cells as vaccine was examined. When radiotherapy and active immunotherapy were combined with SPG, suppression of tumor growth was observed from an early stage in comparison with the group which was not administered SPG. SPG also inhibited the pulmonary metastasis of NR-S1 tumor after radiotherapy.

Animals↗
PubMed1992

Interferon-alpha, interferon-gamma and sizofiran in the adjuvant therapy in ovarian cancer--a preliminary trial.

The study included 24 cases of negative second-look laparotomy (SLL) after operation on ovarian cancer. 12 cases were treated with sizofiran and recombinant interferon-gamma before and after SLL and then with human lymphoblastoid interferon-alpha. The remaining 12 cases (controls) were followed up without any drug therapy after SLL. There were no recurrences in the treated group, but in 3 cases of the control group. Also significant difference in survival was noted in the treated group.

Adult↗
PubMed1996

Augmentation of antitumor effect by combined administration with interleukin-2 and sizofiran, a single glucan, on murine EL-4 lymphoma.

The antitumor effect of the combined administration with recombinant human interleukin-2 (rIL-2) and sizofiran (SPG), a single glucan of Shizophyllum commune Fries, was studied in vivo in C57BL/6 mice intraperitoneally inoculated with EL-4 lymphoma. The effect was evaluated by a) comparing the survival time of the mice, b) analysis of the intraperitoneal cell population in Giemsa-stained specimens, c) surface marker analysis of peritoneal exudative cells with flow cytometry, d) cytotoxic assay of cells against EL-4 and Yac-1 lymphoma, and e) elimination of some cell populations by monoclonal antibodies, to identify the antitumor-effector cells showing cytotoxic activity. The survival of mice given both rIL-2 and SPG was significantly longer than the control mice or those given SPG alone or rIL-2 alone. It was demonstrated that the administration of SPG and/or rIL-2 to the EL-4 lymphoma-bearing mice activated immune-response cells in the peritoneal cavity such as T lymphocytes, NK cells, or macrophages, which might be effective in reducing lymphoma cells. The combination of rIL-2 and SPG administration appears to activate the antitumor-immune response at the tumor site more effectively than when either agent was administered alone.

Animals↗
PubMed1996

Effect of sizofiran on regional lymph nodes in patients with head and neck cancer.

The immunomodulating effects of preoperative sizofiran (SPG) administration on regional lymph nodes were studied in patients with stage III or IV head and neck cancer, by comparing the immunofunction of peripheral blood. The regional lymph nodes were dissected surgically, and freshly obtained mononuclear cells were studied to investigate the interleukin 2 (IL-2) production, the LAK and NK activities, and the quantitative analysis of the surface phenotype of the mononuclear cells. The results indicated that SPG enhanced immunological activities in the regional lymph nodes, as shown by increased IL-2 production and cytotoxic activities of the effector cells (NK, LAK), and increased helper T lymphocytes (CD4+) in the tumor-uninvolved lymph nodes. The immunofunction following SPG administration was attenuated, but was still augmented in the regional lymph nodes with metastases. Therefore, SPG was found to be a biologic response modifier to enhance the immunofunctions of the regional lymph node in patients with head and neck cancer.

Adjuvants, Immunologic↗