Disease relevance of PYRAN COPOLYMER

• In the present study, both MVE-2 or Corynebacterium parvum induced a dramatic augmentation of liver NK activity, which reached maximum levels 3-5 d after treatment [1].
• The growth and metastasis of sc transplanted Lewis lung carcinoma were inhibited in C57BL/6J mice by treatment with pyran copolymer [2].
• 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 [3].
• This study was designed to determine the toxicity and immunological effects of MVE-2 in humans [4].
• Two chemicals, pyran copolymer and glucan, and one biological, Brucella abortus strain 456 ether extract, were shown to be strong stimulators of antitumor immunity [5].

Psychiatry related information on PYRAN COPOLYMER

• However, neither i.v. treatment with MVE-2 nor CSF-1 (20,000 U daily for 4 days) had any pronounced effect on the permissiveness of KC or PMO to infection with HSV-1 [6].

High impact information on PYRAN COPOLYMER

• Factor B represented approximately 0.5% of newly synthesized protein and 4-6% of the secreted protein of resident peritoneal macrophages and macrophages elicited with thioglycollate broth, pyran copolymer, NaIO4, bacillus Calmette-Guerin, or Corynebacterium parvum [7].
• In contrast, apolipoprotein E, another secreted protein of macrophages, was secreted by resident and thioglycollate-elicited macrophages but not by freshly harvested pyran copolymer-activated macrophages [7].
• Experimental chemotherapy (L1210) with 5-aza-2'-deoxycytidine in combination with pyran copolymer (MVE-4), an immune adjuvant [8].
• Effects of combined radiotherapy and immunotherapy with the use of pyran copolymer on murine fibrosarcoma [9].
• Chemoattractant properties of Corynebacterium parvum and pyran copolymer for human monocytes and neutrophils [10].

Chemical compound and disease context of PYRAN COPOLYMER

• We have determined the effect of sheep anti-mouse interferon globulin on the anti-tumor effects of poly I-C, statolon, tilorone, pyran copolymer and BCG in mice inoculated with Ehrlich ascites or L 1210 lymphoma cells [11].
• Similarly, canine cell cultures produced very low concentrations of interferon in response to Newcastle disease virus or polyinosinic-polycytidylic acid and no detectable concentrations of interferon in response to pyran copolymer or tilorone hydrochloride [12].
• 1. Antiviral protection of standard doses of MVE-2, pIC, pICLC, rmIFN-tau and CL246,738 against lethal MCMV or HSV-2 infections was not abrogated by NK cell depletion, demonstrating that NK cells are not required for BRM-induced antiviral activity against these herpesviruses [13].
• Increased therapeutic efficacy and reduced toxicity of doxorubicin linked to pyran copolymer via the side chain of the drug [14].

Biological context of PYRAN COPOLYMER

• Although numbers were small, the enhanced ADCC seemed related to both single dose and cumulative dose of MVE-2 [4].
• The stimulatory effects on myelopoiesis, however, could only be obtained by administering MVE-2 at greater than or equal to 3 days after CY, which correlated with an MVE-2-induced simultaneous increase in granulocyte and/or macrophage colony-stimulating factor secretion by bone marrow cells or M phi [15].
• IC-21 macrophages and primary cultures of pyran copolymer-elicited peritoneal macrophages demonstrated similar tumor binding avidity, kinetics, saturability, and metabolic requirements for optimal high avidity tumor binding [16].
• We therefore compared the pharmacokinetics and in vivo efficacy of SOD with two modified forms of this protein: SOD coupled to the copolymer DIVEMA and mannosylated-SOD [17].
• This conclusion was based on the reduced viabilities of cells treated with both an eliciting agent and an activating agent prior to in vitro treatment with anti-asGM1 + C, as well as by reductions in cytolytic activity of pM phi elicited with peptone and activated by MVE-2, following anti-asGM1 treatment in vitro or administration in vivo [18].

Anatomical context of PYRAN COPOLYMER

• However, compared with primary cultures of pyran copolymer-elicited peritoneal macrophages, IC-21 macrophages bound 4-fold more tumor cells and were more homogeneous for tumor binding capability [16].
• Additional treatment with the chemically defined biological response modifier maleic anhydride divinyl ether copolymer (MVE-2) was able to ameliorate the myelosuppressive effects of CY and to restore normal bone marrow cellularity [15].
• Five of six patients receiving more than 2 g of MVE-2 had improvement in lymphocyte ADCC [4].
• Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days [19].
• The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed [20].

Associations of PYRAN COPOLYMER with other chemical compounds

• We synthesized TNF-alpha conjugated with the copolymer of divinyl ether and maleic anhydride (DIVEMA), which has intrinsic antitumor activity as a synthetic biological response modifier [21].
• The time sequence with which these CY related positive effects on tumor burden and s(Tu)I, as well as the adverse effects on macrophages and hematopoietic functions occurred, gives sufficient explanation for the narrow window in time for successful immunotherapy with MVE-2 after preceding chemotherapy with CY [22].
• To enhance the therapeutic usefulness of antitumor cytokines in vivo, we synthesized bioconjugated tumor necrosis factor-alpha (TNF-alpha) with divinyl ether and maleic anhydride copolymer (DIVEMA), which has intrinsic antitumor activity as a synthetic biological response modifier [23].
• Direct activation in vitro of mouse peritoneal macrophages by pyran copolymer (NSC 46015) [24].
• Immobilization of protein ligands with methyl vinyl ether-maleic anhydride copolymer [25].

Gene context of PYRAN COPOLYMER

• The degree of inhibition of mammalian DNA-dependent RNA polymerases I and II and Moloney leukemia virus RNA-dependent DNA polymerase by pyran copolymer was dependent on the concentration of the divalent cation cofactor in the reaction mixture [26].
• Second, we established that MVE-2 may exert CSF-mediated antitumor effects on certain leukemic tumor cells [27].
• These results suggest that DIVEMA is a useful polymeric modifier for conjugation of TNF-alpha to increase its antitumor activity [21].
• Immune response of BALB/c X DBA/2F1 mice to a tumor allograft during pyran copolymer-induced tumor enhancement [28].
• In vivo treatment with C. parvum (0.7 mg/mouse, i.p., day-3), MVE-2 (25 mg/kg, i.p., day-3), poly I:C (4 mg/kg, i.p., day-3), or IFN (10(5) U/mouse, i.p., day-1) resulted in a marked augmentation and a change of distribution of cytotoxic activity [29].

Analytical, diagnostic and therapeutic context of PYRAN COPOLYMER

• Enhancement of a tumor allograft in BALB/c x DBA/2 F1 mice by pyran copolymer [30].
• Injection of MBL-2 tumor-bearing mice with MVE-2, at 3 days after Cy treatment, caused a decrease in tumor burden and a significant increase in median survival time as compared to treatment with CY alone [15].
• These results suggest several approaches to the clinical application of MVE-2 and provide additional data on the therapeutic activity of the pyran copolymer derivatives in different animal models [31].
• MVE-2 was, therefore, chosen for clinical trials [4].
• Further experiments demonstrated that splenectomy before the administration of MVE-2 did not inhibit the augmentation of liver-associated NK activity [32].

References