SEARCH · PubMed Health

Results for “Pyran Copolymer”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed1979

Mobilization of murine hemopoietic stem cells (HSC) by Pyran Copolymer.

Pyran Copolymer, divinyl-ether maleic anhydride increases the concentration of circulating pluripotential stem cells in mice by a factor of 15 to 30. Maximal mobilization occurs five days after Pyran Copolymer injection with synchronous peaks of CFU-S and CFU-C. When Pyran fractions of defined molecular weight from 12,000 to 52,000 are injected into mice, mobilization of CFU-S and CFU-C parallels molecular weight. Hemopoietic stem cells are mobilized from bone marrow into peripheral blood and subsequently trapped in the spleen.

Animals↗

PubMed1976

Specific potentiation of L1210 vaccine by pyran copolymer.

Pyran copolymer (NSC 46015) was found to potentiate strongly the immune response of C57BL/6J X DBA/2 F1 mice to 10(4) live L1210 tumor cells following suboptimal vaccination with 10(7) radiation-inactivated L1210 cells. Optimal immunity to challenge was produced by concomitant i.p administration of pyran and L1210 vaccine, and activity was dependent upon both pyran and vaccine dosages. In addition, this immunopotentiation seemed to be related to the intrinsic viscosity of different pyran preparations tested, although all the pyran compounds had significant activity. Furthermore, the increased immunity of subsequent live tumor challenge appeared to be specific for the vaccinating cell type.

Animals↗

PubMed1976

Enhancement of a tumor allograft in BALB/c x DBA/2 F1 mice by pyran copolymer.

Pyran copolymer (NSC 46015) was evaluated with respect to its effect on the rejection of a murine leukemic allograft by BALB/c x DBA/2 F1 (CD2F1) mice. Significant prolongation of allograft survival with production of progressively growing lethal tumors was found following pyran administration. This phenomenon occurred at nontoxic doses of the drug and appeared to be closely related to the timing of pyran injection. Nonspecifically stimulated lymphocyte blast transformation by concanavalin A was not impaired by pyran when lymphocytes were exposed in vitro to the drug. The mechanism of tumor allograft enhancement remains obscure but may be related to allograft size at the time of pyran administration.

Animals↗

PubMed1983

Inhibition of DNA-dependent RNA polymerase from Escherichia coli by pyran copolymer.

Pyran copolymer, a potent inhibitor of DNA-dependent RNA polymerase from Escherichia coli, prevented polyribonucleotide synthesis by blocking both the initiation and elongation steps. The inhibition was noncompetitive with respect to template and nucleotide triphosphate substrates. Template binding and the stability of the nascent RNA chain were not affected by the inhibitor.

DNA-Directed RNA Polymerases↗

PubMed1978

Future direction of synthetic polyanions (pyran copolymer).

Pyran copolymer (maleic anhydride-divinyl ether) has consistently reproducible molecular weight-related biologic effects associated with toxic, immunologic antitumor, and antiviral effects. Fortunately, the antitumor action occurs with the least toxic lower molecular weight fraction. Immunoadjuvant effects with this fraction would be critical to its development. Studies of polymers should include evaluation of effects on splenomegaly, splenic esterase changes, lipolysis, reverse transcriptase, nucleases, calcium flux, cyclic nucleotides, and complement and clotting elements.

Animals↗

PubMed1974

Inhibition of RNA-dependent DNA polymerase of avian myeloblastosis virus by pyran copolymer.

PYRAN COPOLYMER, A KNOWN IMMUNOSTIMULATOR, WAS FOUND TO BE A POTENT INHIBITOR OF PURIFIED DNA POLYMERASE (DEOXYNUCLEOSIDETRIPHOSPHATE: DNA deoxynucleotidyltransferase; EC 2.7.7.7) isolated from avian myeloblastosis virus. Unlike other inhibitors, pyran showed unique features of inhibition. It interacts with the polymerase at a region other than the template site. The inhibitory effect was overcome only by excess enzyme and not affected by excess template. The degree of inhibition was not template specific for the templates tested: 70S RNA from avian myeloblastosis virus, synthetic hybrid poly(rA).oligo(dT)(10), synthetic copolymer poly(dA-dT), and activated calf-thymus DNA. The observed rate of inhibition by pyran was shown to vary with the different polymerases tested. Inhibition was shown with all oncornaviral polymerases and, to a lesser extent, with mammalian polymerases. However, two of the three bacterial polymerases, by contrast, showed a marked activation.

Adenine Nucleotides↗

PubMed1987

Increased therapeutic efficacy and reduced toxicity of doxorubicin linked to pyran copolymer via the side chain of the drug.

Doxorubicin was covalently linked to divinyl ether-maleic anhydride copolymer (pyran copolymer) in its polycarboxylate form via the methylketone side chain through a nucleophilic substitution reaction of the 14-bromo derivative of the drug. The drug conjugated to the synthetic polyanionic polymer was tested for antitumor activity in a range of experimental murine tumor systems. When administered ip to mice bearing ip implanted tumors (P388 leukemia or macrophage tumor J774), the polymer-linked drug was superior to free doxorubicin and daunorubicin in increasing the life span of treated animals. Treatment with the conjugate also resulted in an improvement in survival time of mice bearing ascitic M50 tumor, although the effects of a single dose of free drug, in the range of maximum tolerated doses, were marginal. When given iv, the conjugate was more effective than free drug against systemic Gross leukemia. The therapeutic advantage of the polymer-linked doxorubicin over free drug was more marked when a multiple treatment schedule was used. Studies in vitro showed that the drug following covalent fixation to the polymer had only marginally decreased cytotoxicity against HeLa and P388 cells when compared with that of free anthracycline. This effect paralleled the lack of reduction in in vivo potency. Moreover, the covalent linkage of the drug to synthetic polymer reduced drug toxicity. This effect was more marked with the ip route of administration than with the iv route.

Animals↗

PubMed1984

Mobilization of canine hemopoietic stem cells by pyran copolymer (NSC 46015).

Pyran copolymer (NSC 46015), a divinyl ether maleic anhydride of broad spectrum molecular weight, was infused into six normal mongrel dogs. The effect on canine blood and bone marrow colony forming units in culture (CFU-C) was followed over an 11-day period. Significant elevation of circulating CFU-c was noted 2 days after pyran infusion; normalization occurred by day 7 postinfusion. Bone marrow CFU-C were decreased 2 days and 5 days after pyran administration. A further increase in circulating CFU-C was noted when pyran was administered twice, 5 days apart. The mobilizing effect of pyran copolymer appears promising enough to warrant further exploration of blood as a source of hemopoietic stem cells for transplantation purposes.

Animals↗

PubMed1975

Decrease in experimental liver metastasis in mice after treatment with pyran copolymer.

Intravenous injection of pyran copolymer (divinyl ether-maleic anhydride) 24 h prior to intravenous injection of B16 melanoma in C57/BL6 mice greatly decreased the number of liver metastases. If the pyran copolymer was administered 3 days after injection of tumor cells, the number of metastases was not significantly decreased. Pyran copolymer has been reported to stimulate interferon production and increase clearance of particulate matter by the reticuloendothelial system. The results of this experiment suggests an important role played by the reticuloendothelial system in experimental liver metastasis.

Animals↗

PubMed1975

Tumor suppression by pyran copolymer: correlation with production of cytotoxic macrophages.

Intraperitoneal administration of pyran copolymer (pyran-2-succinic anhydride-4,5-dicarboxytetrahydro-6-methylanhydride polymer) protected C3H/HeN male mice against tumor development after intradermal challenge with cells of the transplantable, methylcholanthrene-induced, syngeneic fibrosarcoma 1038. Peritoneal cells from pyran-treated but not from normal animals suppressed tumor development in local passive-transfer experiments. Adherent peritoneal cells from pyran-treated mice were cytotoxic in vitro to several syngeneic murine tumor cell lines including 1038.

Animals↗

PubMed1981

Inhibition of the classical and alternative pathways of human and guinea pig complement by pyran copolymer.

The ability of pyran copolymer to interact with the classical and alternative pathways of complement was assessed in human and C4-deficient guinea pig serum. Pyran induced a dose-dependent inhibition of hemolytic activity in both serum systems. Immuno-electrophoretic analysis of pyran-treated human serum revealed that C3 was not cleaved. Factor B was altered into a more anionic mobility which was not similar to biologically cleaved Ba or Bb fragments. Pyran-treated serum was unable to lyse antibody-coated erythrocytes (EA or EA coated with C1 and C4 and EA coated with C1, C4 and C2. Pretreatment of serum with ethylenediaminetetraacetic acid did not prevent inhibition of hemolytic activity by pyran. Cobra venom factor did not cleave C3 in the presence of pyran. These data indicate that pyran does not activate complement by standard mechanisms but does inhibit one or more of its components.

Animals↗

PubMed1980

Effect of pyran copolymer on murine hemopoiesis.

Pyran Copolymer (NSC-46015), a divinyl-ether maleic anhydride leads to a significant shift in distribution of nucleated cells and CFUs in the bone marrow and spleen. The bone marrow cellularity and the CFUs content reach a nadir 4 to 6 days after Pyran injection, simultaneous rise in spleen cellularity and CFUs concentration of circulating pluripotent stem cells by a factor of 10 to 45 and a concomitant rise of CFUc is seen. the origin of the mobilized pluripotent stem cells is likely to be the bone marrow, not athe spleen.

Animals↗

PubMed1984

Cryptococcus neoformans: in vivo protection of mice by pretreatment with pyran copolymer.

Synthetic polyanions have been shown to alter host resistance to infection. The anticryptococcal effect of pyran copolymer was assessed in vivo and in vitro. Pretreatment with pyran copolymer significantly extended mean survival in mice lethally infected with Cryptococcus neoformans when compared to untreated animals (p less than 0.01). The anticryptococcal effect of peritoneal exudate cells (PEC) elicited by 10% thioglycollate or pyran copolymer (25 mg/kg) was assessed in vitro. Initial percent phagocytosis of both encapsulated and non-encapsulated isolates of C. neoformans was greatest in the pyran elicited PEC. Significant killing of C. neoformans in vitro was observed only in pyran-activated PEC cultures combined with non-encapsulated cells of C. neoformans, although pyran PEC did inhibit initial growth of phagocytized encapsulated yeast cells. The protection of pyran copolymer pretreated mice from infection with C. neoformans, but the absence of significant killing of encapsulated yeast in vitro suggest a complex mechanism of host defense which may involve an activation of the reticuloendothelial system by pyran copolymer.

Animals↗

PubMed1980

Inhibition of purified wheat germ DNA dependent RNA polymerase by pyran copolymer.

The inhibition of DNA and RNA polymerases in vitro by pyran copolymer has been shown to be related to its affinity for divalent cations. The present investigation was designed to explore further the nature of this inhibition using completely purified eukaryotic RNA polymerase II from wheat germ. Inhibition was determined as a function of divalent ion concentration and, as previously seen with less pure enzyme preparation, was greatest at low (Mn2+) and least at higher concentrations. No inhibition was observed at concentrations greater than 4.8 mM MgCl2 in the presence of 10 micrograms pyran/mL. The inhibition by pyran copolymer was exerted immediately unlike other polyanions, such as heparin and polynucleotides. This indicates that it stops RNA chain growth immediately as do known chelators of divalent cations. The size of pyran copolymer was shown to affect the extent of inhibition when different sized polymers were fractionated from a heterogenous single lot. However, when sized fractions were obtained from different lots we could not show a size-dependent inhibition. Although the mechanisms by which pyran copolymer exerts its biological effect is unknown, it may well be related to its association with cations. The inhibition of enzymes requiring these cations appears to be a sensitive method of observing such an association.

DNA-Directed RNA Polymerases↗

PubMed1978

Effects of combined radiotherapy and immunotherapy with the use of pyran copolymer on murine fibrosarcoma.

A weakly immunogenic, 3-methylcholanthrene-induced, subcutaneous fibrosarcoma syngeneic to inbred C3H/HeJ mice was used. Pyran copolymer was injected either directly into the tumor, ip, or iv as soon as tumors appeared or when tumors were 8 mm in diameter. One, three, or five doses of pyran copolymer at 10 or 20 mg/kg/dose were injected, with multiple doses being given every other day. Pyran copolymer injected intratumorally once, three times, or five times significantly retarded tumor growth and prolonged the survival times of the hosts. Of the other routes and doses, only pyran copolymer given three times iv significantly retarded tumor growth, but none of these significantly prolonged the survival times of the hosts. Pyran copolymer alone did not induce any complete regression of tumor. Local tumor irradiation with a single exposure to 2,000 rads of X-ray induced complete regressions in some mice, but a higher percentage of tumor cure was observed when tumor irradiation was followed by pyran copolymer treatment.

Animals↗

PubMed1977

Macrophage involvement in the protective effect of pyran copolymer against the Madison lung carcinoma (M109).

Pyran copolymer (NSC 46015) therapy markedly enhanced host resistance to a murine lung carcinoma (M109) implanted s.c. Multiple dose schedules were not significantly better than single doses at increasing lifespan. Although tumor necrosis was much more extensive in the lesions of pyran-treated mice, pyran copolymer was not directly toxic to M109 cells in vitro. A comparative histopathological study revealed an intense histiocytic reaction in the connective tissue surrounding the primary tumor in mice receiving pyran as compared to 0.9% NaCl solution-treated controls. Macrophages were often associated with necrobiotic tumor cells. Morphologically activated macrophages were recovered from pyran-treated animals which potently inhibited DNA synthesis of M109 tumor cells in vitro. This response peaked 6 days after drug treatment and was to a large extent specific for neoplastic cells. Our results from both in vivo and in vitro studies support the concept that pyran enhances host resistance to neoplasia by mobilization and activation of the reticuloendothelial elements of the host's defense.

Animals↗

PubMed1980

Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer.

Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic-adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran-treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors.

Animals↗

PubMed1983

Effect of pyran copolymer on activation of murine macrophages: evidence for incomplete activation by use of functional markers.

The degree of activation of peritoneal macrophages elicited by pyran copolymer (MVE-2) was studied in C57BL/6J mice. When cytotoxicity was examined under endotoxin-free culture conditions, the pyran-elicited macrophages could not complete cytolysis of tumor target cells. The macrophages, however, completed cytolysis when pulsed with endotoxin. These results were obtained when either the interval between injection of the pyran copolymer and harvest of the macrophage or the dose of pyran was varied. The pyran-elicited macrophages expressed five markers considered to be typical of inflammatory macrophages, and bound tumor cells to an augmented degree. The pyran-elicited macrophages were capable of secreting a potent cytolytic proteinase when pulsed with endotoxin, but did not secrete cytolytic proteinase spontaneously. The pyran-elicited macrophages, in contrast to inflammatory macrophages, could effect cytostasis of tumor cells; their cytostatic potential was also augmented by addition of endotoxin. Taken together, the results indicated that pyran copolymer elicits primed but not fully activated murine macrophages.

Animals↗