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Cancer Immunology, Immunotherapy : CII 1991The 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...
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.
Topics: Animals; Bone Marrow; Cell Division; Cells, Cultured; Fluorouracil; G(M1) Ganglioside; Glycosphingolipids; Killer Cells, Natural; Male; Mice; Mice, Inbred C3H; Sizofiran
PubMed: 1760807
DOI: 10.1007/BF01741319 -
Clinical and Experimental Immunology Nov 1991The effect of SPG on leukocytes has been studied in 20 patients with oral carcinoma and the actions have been analysed in vitro. SPG 1 mg/kg was administered...
The effect of SPG on leukocytes has been studied in 20 patients with oral carcinoma and the actions have been analysed in vitro. SPG 1 mg/kg was administered intramuscularly twice weekly. Peripheral venous blood was collected before, and 1 week and 2 weeks after the initiation of SPG treatment. Both CD16+CD57- and CD16-CD57+ cell populations were significantly increased after treatment, but no T cell subset varied. While enhancement of lymphokine-activated killer activity could not be found, an increase in natural killer (NK) activity was observed in 15 of the subjects, and the mean NK level was significantly increased from an initial 34.7 +/- 18.7% to 46.4 +/- 16.5% after two weeks of injections. O2-production by polymorphonuclear leukocytes (PMNL) was stimulated 6 h after SPG injection. When PMNL were treated in vitro with SPG 32 micrograms/ml, enhanced O2-generation was induced and protein kinase C (PKC) activity in a membrane fraction increased. SPG did not directly affect non-specific PMNL killing of K562 cells or antibody-dependent cell mediated cytotoxicity against Raji cells, but non-specific PMNL killing was enhanced by culture-conditioned medium from peripheral blood mononuclear cells (PBMC) containing 10 micrograms/ml SPG. Interleukin-1 beta, -3, -4, -6, tumour necrosis factor-alpha, granulocyte-macrophage colony stimulating factor and IFN-gamma levels in the conditioned medium were not increased compared with medium from PBMC not treated with SPG. No clear increase of these cytokines was found in serum from the SPG-treated patients. From the above results, enhancement of PMNL O2-generation by SPG seems to be a direct action of SPG, but the mechanism of elevation of the non-specific killing activity of PMNL and NK cells is not known. Perhaps other cytokines than those assayed have participated in increasing non-specific cytotoxicity.
Topics: Antibody-Dependent Cell Cytotoxicity; Calcimycin; Cytokines; Cytotoxicity, Immunologic; Humans; Immunity, Innate; In Vitro Techniques; Killer Cells, Natural; Lymphocyte Subsets; Lymphocytes; Neutrophils; Protein Kinase C; Respiratory Burst; Sizofiran; Superoxides; Tetradecanoylphorbol Acetate; Time Factors
PubMed: 1657462
DOI: 10.1111/j.1365-2249.1991.tb05801.x -
Molecules (Basel, Switzerland) Jan 2023Amphiphilic polysaccharides can be used as wall materials and applied to encapsulate hydrophobic active chemicals; moreover, there is significant demand for novel...
Amphiphilic polysaccharides can be used as wall materials and applied to encapsulate hydrophobic active chemicals; moreover, there is significant demand for novel medical high-molecular-weight materials with various functions. In order to prepare amphiphilic schizophyllan (SPG), octenyl succinic anhydride (OSA) was chosen to synthesize OSA-modified schizophyllan (OSSPG) using an esterified reaction. The modification of OSSPG was demonstrated through FT-IR and thermal analysis. Moreover, it was found that OSSPG has a better capacity for loading curcumin, and the loading amount was 20 μg/mg, which was 2.6 times higher than that of SPG. In addition, a hydrogel made up of PVA, borax, and C-OSSPG (OSSPG loaded with curcumin) was prepared by means of the one-pot method, based on the biological effects of curcumin and the immune-activating properties of SPG. The mechanical properties and biological activity of the hydrogel were investigated. The experimental results show that the dynamic cross-linking of PVA and borax provided the C-OSSPG/BP hydrogel dressing with exceptional self-healing properties, and it was discovered that the C-OSSPG content increased the hydrogel's swelling and moisturizing properties. In fibroblast cell tests, the cells treated with hydrogel had survival rates of 80% or above. Furthermore, a hydrogel containing C-OSSPG could effectively promote cell migration. Due to the excellent anti-inflammatory properties of curcumin, the hydrogel also significantly reduces the generation of inflammatory factors, such as TNF-α and IL-6, and thus has a potential application as a wound dressing medicinal material.
Topics: Hydrogels; Curcumin; Sizofiran; Wound Healing; Succinic Anhydrides; Spectroscopy, Fourier Transform Infrared; Bandages; Anti-Inflammatory Agents
PubMed: 36770985
DOI: 10.3390/molecules28031321 -
The Keio Journal of Medicine Sep 1991Augmentation of anti-tumor effect of interleukin 2 (IL-2) with sizofiran (SPG) was demonstrated with in vivo and in vitro experiments. C3H/He mice with subcutaneously...
Augmentation of anti-tumor effect of interleukin 2 (IL-2) with sizofiran (SPG) was demonstrated with in vivo and in vitro experiments. C3H/He mice with subcutaneously inoculated X5563 tumor were used as experimental models. IL-2 at a dose of 2 X 10(4) units per mouse by subcutaneous injection, and/or SPG at a dose of 0.1 g per mouse by intramuscular injection were given every other day for a total of ten times. Tumor infiltrating lymphocytes (TIL) were investigated with the avidin-biotin peroxidase complex method. Cytotoxic activity of mice spleen cells after the therapies against YAC-1, X5563 and MH134 were tested with 51Cr release assay. IL-2 or SPG alone suppressed tumor growth in vivo, although not significantly. Combination therapy with IL-2 and SPG suppressed tumor growth in vivo significantly (p = 0.04). Mice treated with the combination survived longer than the mice treated with the single drug (p less than 0.05) and the controls (p less than 0.001). Immunohistologically, more TILs were seen in the combination group than the other groups. In the cytotoxicity study, 3 days after initiation of the therapies, augmentation of natural killer (NK) activity was greater by the combination than by IL-2 or SPG alone. After incubation with IL-2, the spleen cells from mice treated with the combination showed higher cytotoxicity against X5563 or MH134 tumors than those treated with the single drug or controls. Obtained results suggested that combination therapy with IL-2 and SPG effectively induced NK cells and lymphokine-activated killer cells in vivo and may lead to greater clinical benefit in the treatment of malignancies.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cytotoxicity, Immunologic; Drug Synergism; Female; Interleukin-2; Killer Cells, Lymphokine-Activated; Lymphocytes; Mice; Mice, Inbred C3H; Neoplasms, Experimental; Sizofiran; Tumor Cells, Cultured
PubMed: 1753556
DOI: 10.2302/kjm.40.132 -
Proceedings of the National Academy of... Feb 2014CpG DNA, a ligand for Toll-like receptor 9 (TLR9), has been one of the most promising immunotherapeutic agents. Although there are several types of potent humanized CpG...
CpG DNA, a ligand for Toll-like receptor 9 (TLR9), has been one of the most promising immunotherapeutic agents. Although there are several types of potent humanized CpG oligodeoxynucleotide (ODN), developing "all-in-one" CpG ODNs activating both B cells and plasmacytoid dendritic cells forming a stable nanoparticle without aggregation has not been successful. In this study, we generated a novel nanoparticulate K CpG ODN (K3) wrapped by the nonagonistic Dectin-1 ligand schizophyllan (SPG), K3-SPG. In sharp contrast to K3 alone, K3-SPG stimulates human peripheral blood mononuclear cells to produce a large amount of both type I and type II IFN, targeting the same endosome where IFN-inducing D CpG ODN resides without losing its K-type activity. K3-SPG thus became a potent adjuvant for induction of both humoral and cellular immune responses, particularly CTL induction, to coadministered protein antigens without conjugation. Such potent adjuvant activity of K3-SPG is attributed to its nature of being a nanoparticle rather than targeting Dectin-1 by SPG, accumulating and activating antigen-bearing macrophages and dendritic cells in the draining lymph node. K3-SPG acting as an influenza vaccine adjuvant was demonstrated in vivo in both murine and nonhuman primate models. Taken together, K3-SPG may be useful for immunotherapeutic applications that require type I and type II IFN as well as CTL induction.
Topics: Adjuvants, Immunologic; Animals; Cells, Cultured; CpG Islands; Enzyme-Linked Immunosorbent Assay; Humans; Immunotherapy; Interferon Inducers; Lectins, C-Type; Leukocytes, Mononuclear; Mice; Mice, Inbred C57BL; Microscopy, Electron; Nanoparticles; Oligodeoxyribonucleotides; Sizofiran; Toll-Like Receptor 9
PubMed: 24516163
DOI: 10.1073/pnas.1319268111 -
International Journal of General... Oct 2010A 69-year-old woman with a history of cervical cancer was admitted to our hospital for further investigation of abnormal shadows on her chest roentgenogram. Histologic...
A 69-year-old woman with a history of cervical cancer was admitted to our hospital for further investigation of abnormal shadows on her chest roentgenogram. Histologic examination of transbronchial lung biopsy specimens revealed epithelioid cell granuloma, and Mycobacterium intracellulare was detected in the bronchial lavage fluid. The plasma level of (1→3)-beta-d-glucan was very high, and this elevated level was attributed to administration of sizofiran for treatment of cervical cancer 18 years previously. Therefore, in patients with cervical cancer, it is important to confirm whether or not sizofiran has been administered before measuring (1→3)-beta-d-glucan levels.
PubMed: 21042427
DOI: 10.2147/IJGM.S12319 -
FEMS Immunology and Medical Microbiology Jul 1998(1 --> 3)-Beta-D-Glucan (beta-glucan) is a biological response modifier that regulates host immune response. However, the side effects of this drug have not been...
(1 --> 3)-Beta-D-Glucan (beta-glucan) is a biological response modifier that regulates host immune response. However, the side effects of this drug have not been extensively examined. In this study, we found that the combination of a beta-glucan and a nonsteroidal anti-inflammatory drug, indomethacin, induced lethal toxicity in mice. Lethal toxicity of orally administered indomethacin (multiple administration to ICR mice; once a day for 2 weeks) was 0/8 (2.5 mg kg(-1)) and 5/8 (5 mg kg(-1)) (death/total) over 2 weeks. The toxicity was enhanced to 3/8 and 8/8 in mice treated with a clinical beta-glucan preparation, sonifilan (250 microg/mouse, single i.p. administration on day 0). A similar effect was observed for other beta-glucans, including SSG, grifolan, zymosan A and zymocel. Enhanced lethal toxicity resulted from a single p.o. administration of indomethacin on day 5 to day 9 after multiple beta-glucans administration. Interferon-gamma, interleukin-6 and colony stimulating factor concentrations in sera of indomethacin/beta-glucan-treated mice were significantly elevated. These results strongly suggest that indomethacin/beta-glucan treatment induces lethality in mice by maladjusting the cytokine network.
Topics: Adjuvants, Immunologic; Animals; Anti-Inflammatory Agents, Non-Steroidal; Colony-Stimulating Factors; Cytokines; Dose-Response Relationship, Drug; Drug Synergism; Glucans; Indomethacin; Interferon-gamma; Interleukin-6; Male; Mice; Mice, Inbred ICR; Sizofiran; Splenomegaly; beta-Glucans
PubMed: 9718206
DOI: 10.1111/j.1574-695X.1998.tb01163.x -
Biological & Pharmaceutical Bulletin Aug 2007Schizophyllan (SPG) is used to treat cervical cancer in combination with irradiation to enhance the immunological surveillance system. Dectin-1 is a cell surface...
Schizophyllan (SPG) is used to treat cervical cancer in combination with irradiation to enhance the immunological surveillance system. Dectin-1 is a cell surface receptor for 1,3-beta-glucan. In this study, we prepared two anti-Dectin-1 monoclonal antibodies, 4B2 and SC30 having a K(D) of 7.04 x 10(-8) M and 1.55 x 10(-7) M, respectively, and evaluated the role of Dectin-1 in SPG-induced anti-tumor activity in mice. Expression of Dectin-1 on peritoneal macrophages and binding of SPG to the cells were decreased by administration of 4B2 and SC30. SPG-mediated anti-tumor activity was inhibited by 4B2 and SC30. 4B2 and SC30 inhibited the binding of SPG to splenocytes from mice. The binding of SPG-biotin to Dectin-1-transfected HEK293 cells was inhibited by 4B2, but not SC30. 4B2 and SC30 differ in their influence on Dectin-1 between primary cells and transduced cells, and Dectin-1 effects 1,3-beta-glucan-mediated anti-tumor activity in mice by binding to SPG.
Topics: Animals; Antibodies, Blocking; Antibodies, Monoclonal; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Biotin; Cells, Cultured; Flow Cytometry; Hybridomas; Lectins, C-Type; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Nerve Tissue Proteins; Peritoneal Cavity; Sizofiran; Spleen; Transfection; beta-Glucans
PubMed: 17666790
DOI: 10.1248/bpb.30.1384 -
International Journal of Molecular... Jun 2021Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family...
Alveolar macrophages are the first line of defense against intruding pathogens and play a critical role in cancer immunology. The Toll-like receptor (TLR) family mediates an important role in recognizing and mounting an immune response against intruding microbes. TLR-9 is a member of the intracellular TLR family, which recognizes unmethylated CG motifs from the prokaryotic genome. Upon its activation, TLR-9 triggers downstream of the MyD-88-dependent transcriptional activation of NF-κB, and subsequently results in abundant inflammatory cytokines expression that induces a profound inflammatory milieu. The present exploratory investigation aimed at elucidating the potency of schizophyllan for entrapping ODN 1826 (SPG-ODN 1826)-mediated stimulation of TLR-9 in provoking an inflammatory-type response in murine alveolar macrophages. Schizophyllan (SPG), a representative of the β-glucan family, was used in the present study as a nanovehicle for endosomal trafficking of CpG ODN 1826. TEM analysis of SPG-ODN 1826 nanovehicles revealed that the prepared nanovehicles are spherical and have an average size of about 100 nm. Interestingly, SPG-ODN 1826 nanovehicles were competent in delivering their therapeutic payload within endosomes of murine alveolar macrophage (J774A.1) cells. Exposure of these nanovehicles within LPS stimulated J774A.1, resulted in a significant provocation of reactive oxygen species (ROS) ( < 0.01) in comparison to CpG ODN 1826 alone. Moreover, the formulated nanovehicles succeeded in generating a profound Th1-based cytokine profile constituted by enhanced expression of IFN-γ ( < 0.001) and IL-1β ( < 0.001) inflammatory cytokines. These findings clearly indicated the immunostimulatory potential of SPG-ODN 1826 nanovehicles for inducing the Th1-type phenotype, which would certainly assist in skewing M2 phenotype into the much-desired M1 type during lung cancer.
Topics: Animals; Cell Survival; Cytokines; Endosomes; Immunophenotyping; Inflammation Mediators; Macrophage Activation; Macrophages, Alveolar; Mice; Nanostructures; Oligodeoxyribonucleotides; Particle Size; Sizofiran; Toll-Like Receptor 9
PubMed: 34202080
DOI: 10.3390/ijms22136833 -
Biophysical Journal Jul 2007Schizophyllan is a beta(1-->3)-D-glucan polysaccharide with beta(1-->6)-branched lateral glucose residues that presents a very stiff triple-helical structure under most...
Schizophyllan is a beta(1-->3)-D-glucan polysaccharide with beta(1-->6)-branched lateral glucose residues that presents a very stiff triple-helical structure under most experimental conditions. Despite the remarkable stability of this structure (which persists up to 120 degrees C in aqueous solution), schizophyllan undergoes a major change of state around 7 degrees C in water that has been hypothesized to result from an order-disorder transition in the lateral residues. This hypothesis is only supported by indirect experimental evidence and detailed knowledge (at the atomic level) concerning hydrogen-bonding networks, interactions with the solvent molecules, orientational freedom of the lateral residues, and orientational correlations among them is still lacking. In this study explicit-solvent molecular dynamics simulations of a schizophyllan fragment (complemented by simulations of its tetrasaccharide monomer) are performed at three different temperatures (273 K, 350 K, and 450 K) and with two different types of boundary conditions (finite nonperiodic or infinite periodic fragment) as an attempt to provide detailed structural and dynamical information about the triple-helical conformation in solution and the mechanism of the low-temperature transition. These simulations suggest that three important driving forces for the high stability of the triple helix are i), the limited conformational work involved in its formation; ii), the formation of a dense hydrogen-bonding network at its center; and iii), the formation of interchain hydrogen bonds between main-chain and lateral glucose residues. However, these simulations evidence a moderate and continuous variation of the simulated observables upon increasing the temperature, rather than a sharp transition between the two lowest temperatures (that could be associated with the state transition). Although water-mediated hydrogen-bonded association of neighboring lateral residues is observed, this interaction is not strong enough to promote the formation of an ordered state (correlated motions of the lateral residues), even at the lowest temperature considered.
Topics: Biophysical Phenomena; Biophysics; Carbohydrate Conformation; Carbohydrate Sequence; Hydrogen Bonding; Models, Molecular; Schizophyllum; Sizofiran; Solvents; Thermodynamics; Water
PubMed: 17237195
DOI: 10.1529/biophysj.106.086116