Activity of (-)-2'-deoxy-3'-oxacytidine (BCH-4556) against human tumor colony-forming units

BACKGROUND: BCH-4556 ((-)-2'-deoxy-3'-oxacytidine) is an L-nucleoside analogue shown to have broad preclinical anti-cancer activity, particularly against solid neoplasms such as prostate, renal, and hepatoma in vitro and in vivo, in contrast to cytosine arabinoside (ara-C) which is preferentially active against leukemia. MATERIALS AND METHODS: The antitumor activity of BCH-4556 was evaluated using human tumor colony-forming unit (HTCFU) assay, in which fresh tumor specimens were taken directly from patients with and without prior chemotherapy. RESULTS: Overall, in vitro responses (50% or less survival compared to untreated controls) were observed in 11% (two of 18), 29% (five of 17) and 50% (nine of 18) of specimens treated for one hour with BCH-4556 at 1, 10 and 100 micrograms/ml, respectively; and 16% (nine of 55), 32% (24 of 74), 48% (35 of 73) and 65% (11 of 17) of specimens treated continuously with BCH-4556 at 0.1, 1, 10 and 100 micrograms/ml, respectively. With the one-hour schedule, a significant difference in response rates was noted between 100 micrograms/ml and 1 microgram/ml (P = 0.02). With the continuous schedule, significant differences in response rates were observed between 1 microgram/ml and 0.1 microgram/ml (P = 0.02), between 10 micrograms/ml and 0.1 microgram/ml (P = 0.0001), as well as between 10 micrograms/ml and 1 microgram/ml (P = 0.01). A trend suggesting the superiority of continuous exposure was observed in paired specimens (n = 18) at comparable drug concentrations. Activity was noted against ovarian (nine of 16 = 56%), renal (three of four = 75%), and melanoma (two of two = 100%) HTCFU at 10 micrograms/ml using the continuous schedule. Comparisons between BCH-4556 and paclitaxel were made in 32 specimens at 10 micrograms/ml using the continuous exposure. Twenty-three specimens showed similar responses with both drugs; seven showed better responses with BCH-4556; and two showed better responses with paclitaxel (P = 0.18). CONCLUSIONS: Promising activity was observed with BCH-4556 against ovarian, renal, and melanoma HTCFU. There appeared to be a positive relationship between BCH-4556 concentration and response using both one-hour and continuous exposures. Continuous exposure to BCH-4556 provided high response rates especially at concentrations above 10 micrograms/ml. For both one-hour and continuous exposures, BCH-4556 had similar, and at times, greater potency than paclitaxel against the same tumor specimens in the present study.     

Long-term residues arising from 14CO2 fixation in swine tissues

Pigs injected intramuscularly with ¹⁴C sodium earbonate solution were killed after 9 and 21 days. The protein hydrolysate from liver tissues were treated with ninhydrin to liberate CO₂ which was used for determination of residual radioactivity. Most of the ¹⁴C from the fixed CO₂ was liberated by this treatment, which was considered to be a suitable method for estimating long-term residues of ¹⁴C in tissues arising from a ¹⁴CO₂ fixation process. The proportion of ¹⁴C in various amino acids remained almost constant over the period of the test.     

Die kristallinität von äthylen-vinylacetat-copolymeren

Copolymers of ethylene and vinyl acetate of different composition were investigated by differential thermal and x-ray analysis in the temperature range of ?80 to 140°C. Compounds with more than 60 weight-% of vinyl acetate are amorphous. In the partially crystalline copolymers with lower contents of vinyl acetate the glass transition temperature is independent of composition and lies below that in amorphous copolymers. The melting points of the partially crystalline compounds increase with ethylene contents and can be described with the aid of a modified FLORY equation. The increase of the degree of crystallinity with ethylene content is demonstrated. The influence of thermal pre-treatment on the melting behaviour is discussed.     

Zum Mechanismus der thermischen Abspaltung von Chlorwasserstoff aus Polyvinylchlorid. 9. mitt.: Zur struktur der verzweigungen in polyvinylchlorid

The reduction of PVC and of copolymers from vinyl chloride and 2-chloropropene with lithium aluminium hydride occurs in a nearly quantitative manner. A selective reduction of the tertiary chlorine atoms in the copolymers, using lithium deuteride, cannot be observed by means of n.m.r. spectroscopy. The amount of CH₃-groupins the reduced samples was determined by i.r. spectroscopic compensation against polymethylene. The number of methyl groups determined in the copolymers agrees well with the copolymer composition found by n.m.r. spectroscopy. The experimental results of the determination of branches and of the thermal degradation indicate no tertiary chlorine atoms in PVC; therefore, one can assume another structure of branches in PVC.     

Dynamisch-mechanische Untersuchungen an Polymerisatgemischen aus Polyäthylacrylat und polymethylmethacrylat

The temperature dependence of damping and modulus has been measured in shear at about 1 Hz for a mixture of polyethylacrylate (PäA) and polymethylmethacrylate (PMMA) which was prepared by mixing the aqueous dispersions of the homopolymers with a particle size of about 100 nm in diameter. Between the wellknown damping peaks of PÄA and PMMA an intermediate peak was found which is ascribed to interactions of the PÄA- und PMMA-segments in the vicinity of the phase boundaries. If the mixture is annealed above the transition temperature of PMMA, this peak vanishes, because the amount of the phase surface is reduced. At temperatures between the transitions of PAA and PMMA the dynamic shear modulus of mixtures PÄA/PMMA is determined by a glassy and a rubbery phase. In addition to the ratio of components this value is considerably influenced by the phase structure. If the polymer mixture is prepared by polymerizing AA in the presence of PMMA, it is shown by comparing the results of calculations based on a simple model with experimentally determined values of the shear modulus, that the glassy PMMA already exists as a continuous phase at a concentration of only 15 wt-%. Electron micrographs confirm this result. If the rubbery PÄA-phase is crosslinked, the elongation at break of such substances is increased 15-fold to about 150%.     

Anwendung der FMIR-Technik zur infrarotspektroskopischem Identifizierung von beschechteten Folien und Papieren

The high efficiency of FMIR-technique by infrared investigations of coated foils, papers and cartons is shown in some examples. In this method the surface of the sample to be investigated which is pressed on both sides of a KRS-5 crystal is scanned repeatedly by the IR-beam. This investigation shows that the reflectance technique yields spectra of higher quality (= resolution + band depth) than the traditional transmittance technique. Moreover the procedure of pressing can be omitted in the investigation of lacquered foils or foils with a smooth surface before recording the spectra. This proved to be necessary according to our results we received by the FMIR investigation of coated papers. Often better spectra of foils are obtained if a FMIR-erystal with 15 reflections is used (angle of incidence 60°). The FMIR-method has the great advantage of simplicity and speed.     

Probleme des abbaus an folienbildenden thermoplastischen hochpolymeren

The mass-produced thermoplastics, PVC, polystyrene and polyolefins, have increasingly gained ground in fields of application where, during and after use, they are subjected as thin layers, e.g. in the form of films, to normal environmental influences. Degradation reactions on thin layers caused by heat and light in the presence of oxygen are gaining importance as much as a “controlled autoxidation” might open up new fields of application. Initiation and acceleration of autoxidation by ?potential sensitizers”? in the presence of oxygen and beams of light are critically evaluated with a view towards desired degradability.     

Kohlenstoffäden

Since a few years the development of carbon fibres from polyacrylonitrile (PAN) is concentrated in particular on improvements of the stabilization stage, i.e. of the early stage of the thermal degradation of PAN. The chemical and physical changes of PAN in the temperature range from 150 to 350°C influencing the properties of carbon fibres are discussed. According to the complex reaction process there exists a variety of possible technical procedures. In conformity with the actual knowledge it may be advantageous to substitute the usual stabilization treatment of PAN in air by a catalytic treatment in fluid reaction mediums. Nitroaromatic compounds in the presence of SnCI₄ adducts are most suited for this purpose. In this way a remarkable shortening of the stabilization time is realized without diminishing the quality of the resulting carbon fibres.     

Zum Verhalten von Polyamidcarbonsäuren aus Pyromellithsäuredianhydrid und Benziding in Lösung. I. Streulicht- und Viskositätsmessungen in Dimethylacetamid

Poly(amic acids) of M _w = 48000 to 434000 were prepared by Polycondensation of pyromellitic dianhydride (PMDA) and benzidine using different stoichiometric ratios of the monomers. The poly(amic acids) were investigated through light scattering and viscosity measurements in dimethylacetamide solutions. In solutions containing LiBr, the polyelectrolyte effects are completely supressed; it is therefore possible to determine the molecular weights, the end-to-end distances and the second virial coefficients. The viscosity equation for poly(amic acid) from PMDA and benzidine in LiBr-dimethylacetamide is as follows: [η] = 3,40 × 10^?2 × M _w^0,78 ml/g. The relatively high [η]-values or correspondingly the low coil densities indicate a loose coiling of the poly(amic acid) molecules. As it is shown by the comparison of the unperturbed dimensions of these poly(amic acids) with the corresponding Avalues of other polymers, the loose coiling of the poly(amic acid) molecules is caused not only through the strong solvation of the polymer molecules by the solvent, but also through the long and stiff benzidine-units in the chain. In LiBr-free dimethylacetamide the beginning dissoziation of the COOH-groups has been noticed through decrease in the intensity of the scattered rays with decreasing angles of observation in the region of small angles and low concentrations. This effect is interpreted by external interferences of the scattered rays, caused by a more regular distribution of the macromolecules in the solutions. The intramolecular interaction of the negative charges produced by the dissoziation of the COOH-groups causes in LiBr-free systems a certain widening of the coil, which is noticed on the higher [η]-values as compared to the systems containing LiBr. As shown by the increase in the optical anisotropy in solutions without LiBr, a change in the coil configuration on the dilution takes place in such a way that it leads to an increase in the ratio of the ellipsoid axis, eventually joined with a geometical widening of the coil.