Controlling transduction and replication of oncolytic adenoviruses

Despite progress in conventional cancer treatment regimes, metastatic disease essentially remains incurable and new treatment alternatives are needed. Virotherapy is a relatively novel approach in cancer treatment. It harnesses the natural ability of oncolytic viruses to kill the cells they proliferate in and to spread to neighboring cells, thereby amplifying the therapeutic effect of the initial input dose. The use of replicating, oncolytic viruses for cancer treatment necessitates introduction of various genetic modifications to the viral genome, thereby restraining replication exclusively to tumor cells and eventually obtaining selective eradication of the tumor without side effects to healthy tissue. Furthermore, various modifications can be applied to the viral capsid in hope of gaining effective transduction of target tissue. In other words, the entry of viruses into tumor tissue can be augmented by allowing the virus to utilize non-native receptors for entry. Genetic capsid modifications may also help to avoid some major hurdles in systemic delivery that ultimately lead to the rapid clearance of the virus from the blood and virus induced toxicity. In addition to genetic modifications that alter the phenotype of the virus, some pharmacologic agents may be utilized to enhance the virus entry to target site. Liver kupffer cells (KC) are responsible for the majority of viral clearance after systemic viral delivery and they play a major role in adenovirus induced acute toxicity. The therapeutic window could possibly be widened by transiently depleting KCs, allowing smaller viral input doses and diminishing KC related toxicity. The transductional efficacy of various capsid modified viruses was analyzed in vitro and in vivo in murine orthotopic breast cancer model. The effect of capsid modifications on the oncolytic efficacy, i.e. the ability of the viruses to kill cancer cells, was evaluated in vitro and in vivo in murine cancer models. We concluded that capsid modifications result in transductional enhancement, and that enhanced transduction translates into more potent oncolysis in vitro and in vivo. When KC depleting agents were used in vivo prior to viral injections, enhanced tumor transduction was seen, but this effect was not translated into enhanced antitumor activity. Transcriptional regulation of replicative oncolytic viruses is a prerequisite for virotherapy. Tumor or tissue specific promoters can be used to control the transcription of adenoviral early genes to gain cancer specific viral replication. Specific deletions in viral regions essential for virus replication in normal cells can further increase the safety by allowing viral genome replication in cancer cells featuring specific mutations. Genetically modified viruses were shown to be able to kill putative cancer stem cells that are thought to be responsible for post treatment relapses and metastasis. Further, pharmacologic intervention reduced viral replication and thereby might offer an additional safety switch in case viral replication related side effects are encountered.

Thermochemistry and lower combustion limit of ammonium perchlorate in presence of methylammonium perchlorates

The heats of combustion of mono-, di-, tri- and tetramethylammonium perchlorates have been determined by bomb calorimetry. The data have been used to explain why the thermal behavior of ammonium perchlorate (AP) is considerably modified in presence of these compounds as shown by differential thermal analysis. Above a particular concentration of methylammonium perchlorate (MAP), AP ignites in a single step around 290°C. The minimum concentration of a MAP (mono-, di-, tri- or tetra-) needed to cause ignition of AP in a single step depends on intramolecular “elemental stoichiometric coefficient” of the mixtures that has the same value regardless of the MAP. Furthermore, the calorimetric values of these mixtures are the same. The heat evolved on ignition of such a composition appears to determine the lower concentration limit of combustion of its mixture with AP.

Thermal reactivity of metal acetate hydrazinates

Metal acetate hydrazinates, M(CH3COO)2(N2H4)2 (M = Mn, Co, Ni, Zn, Cd) have been prepared and characterized by chemical analysis and infrared absorption spectra. Thermal decomposition of the complexes has been studied using simultaneous TG-DTG-DTA technique. Metal acetate hydrazinates decompose exothermically through metal acetate intermediates to the respective metal oxides.

Pyrolysis and combustion of alpha-cellulose: effect of dihydrazinium phosphate (N2H5)2HPO4

A strip of Whatman filter paper (α-cellulose) dipped in an aqueous solution of dihydrazinium phosphate, (N2H5)2HPO4(DHP), and dried, carbonized without flame when ignited. The observed flame retardancy of DHP on α-cellulose has been studied using TG, DTA and mass spectrometry. Dihydrazinium phosphate appears to catalyze the dehydration of α-cellulose, minimizing the depolymerization which produces flammable tars, with the formation of water and char. Flame retardancy of DHP is compared with that of diammonium phosphate and phosphoric acid.

Low temperature ferrite formation using metal oxalate hydrazinate precursor

Magnesium ferrite, MgFe2O4 has been prepared at low temperatures by the thermal decomposition of a new precursor, MgFe2(C2O4)3. 5N2H4. The ferrite has been characterized by X-ray diffraction, infrared and Mössbauer spectra.

Thermal reactivity of metal oxalate hydrazinates

Metl oxalate hydrazinates MC2O4·2 N2H4 where M=Mg, Mn, Fe, Co, Ni, Cu, Zn and Cd have been prepared and characterised by chemical analysis and infrared spectra. Thermal reactivity and decomposition of these oxalato complexes have been studied using thermogravimetry and differential thermal analysis. Hydrazinates of Mn, Fe, Co, Ni and Cu oxalates exhibit autocatalytic decomposition behaviour whereas the others do not. This phenomenon can be attributed to the presence of a bridged hydrazine as well as the thermal stability of the anhydrous metal oxalates.

A one-step process for the preparation ofγ-Fe2O3

Abstract is not available.

Thermal analysis of metal sulfate hydrazinates and hydrazinium metal sulfates

Thermal analysis of metal sulfate hydrazinates, MSO4·xN2H4 (I) (M=Mn, Co, Ni, Zn, Cd; x = 2–3), hydrazinium metal sulfates, (N2H5)2M(SO4)2 (II) (M=Mn, Cu, Zn, Cd), and N2H5LiSO4 have been studied using simultaneous TG-DTGDTA. Both types of complexes, I and II, decompose to the respective metal sulfates or a mixture of metal sulfide and sulfate.

A formal synthesis of 18-hydroxyestrone

A formal synthesis of Image -18-hydroxyestrone has been achieved by the preparation of Image -3-methanesulfonyloxy-13β,17β-dicarboxy-18--norestra-1,3,5(10)-triene anhydride, the dextrorotatory enantiomer of which is an intermediate in Barton's conversion of Image -estrone to Image -1β-hydroxyestrone (KC-6A).

Thermal decomposition of hydrazinium aluminium sulfate hydrate and hydrazinate

As a part of our research programme on hydrazine derivatives [I-4]. we have prepared a number of hydrazinium metal sulfates [ 1.S] (N2 H5), M(SO4)2, where M = Mn, Fe, Co, Ni, Cu. Zn, Cd and Mg and their hydrazine adducts [2] of the type (N2H5)2M(SO4)2 . 3 N2H4. where M = Fe, Co and Ni, as well as N2H5AI(SO4)2 . 6N2H4. Recently, we reported [5.6] the thermal analysis of these compounds. Our .literature survey on the thermal analysis of alums [7] and aluminium salts [8] indicated that, although the preparation of hydrazinium aluminium sulfate dodecahydrate, N2H5Al(SO4)2 . 12 H2O, has been reported [9], there appears to be no report on its thermal analysis. Here, we report the results df the thermal analysis of N2H5Al(SO4)2 . 12 H2O and N2H5Al(SO4)2 . 2N2H4.

Thermal analysis of hydrazine perchlorate hydrates and ammoniates

Abstract is not available.

Synthesis and Characterisation of Metal Hydrazine Nitrate, Azide and Perchlorate Complexes

Metal hydrazine nitrate complexes of the type M(N2H4)Nn (NO3)2 where M = Mg, n = 2; M = Mn, Fe, Co, Ni, Zn and Cd and n = 3; metal dihydrazine azide complexes of the type M(N2H4)2 (N3)2 where M = Mg, Co, Ni and Zn; and Mg(N2H4)2 (C1O4)2 have been prepared by dissolving the respective metal powders in the solution of corresponding ammonium salts (NO3, N3 and C1O4) in hydrazine hydrate. These hydrazine complexes were also prepared by the conventional method involving the addition of alcoholic hydrazine hydrate to the aqueous solution of metal salts. The hydrazine complexes have been characterised by chemical analysis, infrared spectra and differential thermal analysis (DTA). Impact sensitivities of hydrazine complexes were determined by the drop weight method. The reactivity of these hydrazine complexes does not change with the method of preparation.

Unsteady Motion of a Stratified Rotating Viscous Fluid between Two Disks

Abstract is not available.

A formal synthesis of 18-hydroxyestrone

A formal synthesis of -18-hydroxyestrone has been achieved by the preparation of -3-methanesulfonyloxy-13β,17β-dicarboxy-18--norestra-1,3,5(10)-triene anhydride, the dextrorotatory enantiomer of which is an intermediate in Barton's conversion of -estrone to -1β-hydroxyestrone (KC-6A).