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Nitrosourea-misonidazole combination chemotherapy: effect on KHT sarcomas, marrow stem cells and gut.

C3H/HeJ mice bearing i.m. transplanted KHT sarcomas were treated with varying doses of either 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) or 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin; CHLZ) as single agents or in combination with 1 mg/g of the chemical radiosensitizer, misonidazole (MISO). Using an in vivo-in vitro tumour-excision assay, the administration of MISO simultaneously with or 3 h after low doses of BCNU (less than 20 mg/kg) was found to give a dose-modification factor (DMF) of approximately 1.65 relative to BCNU alone. At higher doses of BCNU, there was less enhancement of cell kill. The DMF for tumour growth delay was likewise dependent on BCNU dose, continuously decreasing with increasing BCNU dose. In contrast, the anti-tumour activity of CHLZ, assessed by both clonogenic cell survival and tumour-growth delay, was not significantly enhanced by the addition of MISO. The enhancement of gastrointestinal toxicity and haematotoxicity by BCNU-MISO combinations was assessed by LD50/7 and CFU-S assays, respectively. MISO enhanced BCNU marrow toxicity by a factor of 1.2-1.3, whilst gut toxicity was enhanced by a factor of approximately 1.2

In vivo response of KHT sarcomas to combination chemotherapy with radiosensitizers and BCNU.

Female C3H/HeJ mice bearing intramuscularly transplanted KHT sarcomas were treated with a single dose of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU, 30 mg/kg, i.p.) alone or in combination with a single dose of misonidazole (MISO, 1.0 mg/g, i.p.) or its desmethylated metabolite Ro-05-9963 (2.0 mg/g, i.p.). The effectiveness of drug therapy was assessed by a tumour growth-delay assay (i.e. measuring the median time required for tumours to grow to treatment size x 4). The relative efficacy of administering the nitroimidazoles in various schedules ranging from 12 h before to 12 h after BCNU administration also was evaluated. Untreated control KHT tumours grew to the initial size x 4 in a median time of 4 days. No significant growth delay was seen in mice treated with either nitroimidazole alone, whilst treatment with BCNU alone produced a median growth delay of 7 days. Combination chemotherapy with 9963 administration 3 h after BCNU significantly increased the median tumour growth delay to 9 days. However, no significant growth delay was produced in any of the other combinations of these agents. The median growth delay was significantly reduced to 5 days when MISO was administered 3 h before BCNU, whereas MISO administered simultaneously 3,6, or 12 h after BCNU significantly enhanced delays ( 9 days). These results indicate that both MISO and 0063 may be combined with conventional therapeutic agents, in this particular case a nitrosourea, to produce an enhanced tumour response. The production of such a response appears to be nitroimidazole as well as schedule dependent

Resolved magnetic structures in the disk-halo interface of NGC 628

Magnetic fields are essential to fully understand the interstellar medium (ISM) and its role in the disk-halo interface of galaxies is still poorly understood. Star formation is known to expel hot gas vertically into the halo and these outflows have important consequences for mean-field dynamo theory in that they can be efficient in removing magnetic helicity. We perform new observations of the nearby face-on spiral galaxy NGC 628 with the Karl G. Jansky Very Large Array (JVLA) at S-band and the Effelsberg 100-m telescope at frequencies of 2.6 GHz and 8.35 GHz. We obtain some of the most sensitive radio continuum images in both total and linearly polarised intensity of any external galaxy observed so far in addition to high-quality images of Faraday depth and polarisation angle from which we obtained evidence for drivers of magnetic turbulence in the disk-halo connection. Such drivers include a superbubble detected via a significant Faraday depth gradient coinciding with a HI hole. We observe an azimuthal periodic pattern in Faraday depth with a pattern wavelength of 3.7$\pm$ 0.1 kpc, indicating Parker instabilities. The lack of a significant anti-correlation between Faraday depth and magnetic pitch angle indicates that these loops are vertical in nature with little helical twisting, unlike in IC 342. We find that the magnetic pitch angle is systematically larger than the morphological pitch angle of the polarisation arms which gives evidence for the action of a large-scale dynamo where the regular magnetic field is not coupled to the gas flow and obtains a significant radial component. We additionally discover a lone region of ordered magnetic field to the north of the galaxy with a high degree of polarisation and a small pitch angle, a feature that has not been observed in any other galaxy so far and is possibly caused by an asymmetric HI hole.Comment: 25 pages, Accepted for publication in Astronomy and Astrophysic

Radio haloes in nearby galaxies modelled with 1D cosmic-ray transport using SPINNAKER

We present radio continuum maps of 12 nearby ($D\leq 27~\rm Mpc$), edge-on ($i\geq 76^{\circ}$), late-type spiral galaxies mostly at $1.4$ and 5 GHz, observed with the Australia Telescope Compact Array, Very Large Array, Westerbork Synthesis Radio Telescope, Effelsberg 100-m and Parkes 64-m telescopes. All galaxies show clear evidence of radio haloes, including the first detection in the Magellanic-type galaxy NGC 55. In 11 galaxies, we find a thin and a thick disc that can be better fitted by exponential rather than Gaussian functions. We fit our SPINNAKER (SPectral INdex Numerical Analysis of K(c)osmic-ray Electron Radio-emission) 1D cosmic-ray transport models to the vertical model profiles of the non-thermal intensity and to the non-thermal radio spectral index in the halo. We simultaneously fit for the advection speed (or diffusion coefficient) and magnetic field scale height. In the thick disc, the magnetic field scale heights range from 2 to 8 kpc with an average across the sample of $3.0\pm 1.7~\rm kpc$; they show no correlation with either star-formation rate (SFR), SFR surface density ($\Sigma_{\rm SFR}$) or rotation speed ($V_{\rm rot}$). The advection speeds range from 100 to $700~\rm km\,s^{-1}$ and display correlations of $V\propto \rm SFR^{0.36\pm 0.06}$ and $V\propto \Sigma_{\rm SFR}^{0.39\pm 0.09}$; they agree remarkably well with the escape velocities ($0.5\leq V/V_{\rm esc}\leq 2$), which can be explained by cosmic-ray driven winds. Radio haloes show the presence of disc winds in galaxies with $\Sigma_{\rm SFR} > 10^{-3}~\rm M_{\odot}\,yr^{-1}\,kpc^{-2}$ that extend over several kpc and are driven by processes related to the distributed star formation in the disc.Comment: 39 pages, 20 colour figures, 10 tables. Accepted by MNRA