Chemosensitivity of prostatic tumour cell lines under conditions of G2 block abrogation.

Conventional chemotherapy has had very limited success in the control of hormone-refractory prostate cancer. Methylxanthine derivatives, such as pentoxifylline (PTX), are known to abrogate the G2 block and enhance the toxicity of ionising irradiation and chemotherapeutic agents. It is now also established that late addition of the cytotoxic drug after irradiation under conditions of G2 block abrogation sensitises human tumour cells for cytotoxins. Here we assess whether the chemosensitivity of prostate tumour cell lines can be enhanced by the application of a low dose of drug in conjunction with a G2 block abrogator. Prostate cell lines DU145, BM1604 and LNCaP were irradiated with 7 Gy 60Co gamma-irradiation. A sub-toxic (2 mM) dose of pentoxifylline and a cytotoxic drug were added at maximum expression of the G2 cell cycle block and cell survival was determined by colony assay. Cisplatin, etoposide and vinblastine were tested at a toxic dose of 10% (TD10). In the TP53 mutant cell lines, DU145 and BM1604, dose enhancement factors (EFs) were found to be in the region of 4.20 for cisplatin, 3.70 for vinblastine, and 3.20 for etoposide. In the TP53 wild-type cell line, LNCaP, the enhancement factors were low and in the region of 1.20 for cisplatin, vinblastine and etoposide. It is clear, therefore, that toxicity enhancement factors (EFs) are greater in the TP53 mutant cell lines, DU145 and BM1604, than in the TP53 wild-type cell line, LNCaP. The results indicate that a significant enhancement of drug toxicity can be obtained if the cytotoxic drug is given under conditions of G2 block abrogation. The sensitisation of prostate cancer cells to cytotoxic drugs is particularly high in radiation-resistant TP53 mutant tumour cells. Drugs which abrogate G2 block have the potential to enhance the therapeutic index and therefore reduce the toxicity of chemotherapy drugs.

Abrogation of G(2)/M-phase block enhances the cytotoxicity of daunorubicin, melphalan and cisplatin in TP53 mutant human tumor cells.

Irradiation of human melanoma (MeWo, Be11) and squamous cell carcinoma (4451, 4197) cells induces cell cycle blocks from which the cells recover to re-enter mitosis after 40-60 h. In the TP53 mutant cell lines, MeWo and 4451, irradiation induces a G(2)-phase block, where the fraction of cells in G(2) phase reaches a maximum after 18-20 h. In the TP53 wild-type cell lines, 4197 and Be11, a G(1)- and G(2)-phase block is reached 12 and 16 h postirradiation, respectively. Addition of pentoxifylline after irradiation at the time when the number of cells in G(2) phase has reached a maximum shortens the normal recovery from G(2)-phase block to approximately 7 h. Addition of daunorubicin, melphalan and cisplatin under these conditions markedly enhanced drug toxicity. In the TP53-mutated cell lines MeWo and 4451, the survival ratio at 7 Gy measured by colony formation was 2.3-2.8, 8.6-85 and 52-74 for daunorubicin, melphalan and cisplatin, respectively. In the TP53 wild-type cell lines, the corresponding survival ratios were found to be 1.3-1.4, 2.3-3.0 and 1.2-2.6, respectively. The survival ratios are for clonogenic survival after 7 Gy and 2 mM pentoxifylline and measure the influence of drug doses that ensure 95% survival in nonirradiated controls. The results indicate that the G(2)-phase block is a crucial event in the damage response that can be manipulated to achieve a significant enhancement of drug toxicity. These effects are particularly pronounced in TP53 mutant cells and are observed at drug doses well below the clinical range.

Lunar Prospector: overview.

Lunar Prospector is providing a global map of the composition of the moon and analyzing the moon's gravity and magnetic fields. It has been in a polar orbit around the moon since 16 January 1998. Neutron flux data show that there is abundant H, and hence probably abundant water ice, in the lunar polar regions. Gamma-ray and neutron data reveal the distribution of Fe, Ti, and other major and trace elements on the moon. The data delineate the global distributions of a key trace element-rich component of lunar materials called KREEP and of the major rock types. Magnetic mapping shows that the lunar magnetic fields are strong antipodal to Mare Imbrium and Mare Serenitatis and has discovered the smallest known magnetosphere, magnetosheath, and bow shock complex in the solar system. Gravity mapping has delineated seven new gravity anomalies and shown that the moon has a small Fe-rich core of about 300 km radius.

Global elemental maps of the moon: the Lunar Prospector gamma-Ray spectrometer.

Lunar Prospector gamma-ray spectrometer spectra along with counting rate maps of thorium, potassium, and iron delineate large compositional variations over the lunar surface. Thorium and potassium are highly concentrated in and around the nearside western maria and less so in the South Pole-Aitken basin. Counting rate maps of iron gamma-rays show a surface iron distribution that is in general agreement with other measurements from Clementine and the Lunar Prospector neutron detectors.

Fluxes of fast and epithermal neutrons from Lunar Prospector: evidence for water ice at the lunar poles.

Maps of epithermal- and fast-neutron fluxes measured by Lunar Prospector were used to search for deposits enriched in hydrogen at both lunar poles. Depressions in epithermal fluxes were observed close to permanently shaded areas at both poles. The peak depression at the North Pole is 4.6 percent below the average epithermal flux intensity at lower latitudes, and that at the South Pole is 3.0 percent below the low-latitude average. No measurable depression in fast neutrons is seen at either pole. These data are consistent with deposits of hydrogen in the form of water ice that are covered by as much as 40 centimeters of desiccated regolith within permanently shaded craters near both poles.

The surface of Mars: the view from the viking 2 lander.

Viking 2 lander began imaging the surface of Mars at Utopia Planitia on 3 September 1976. The surface is a boulder-strewn reddish desert cut by troughs that probably form a polygonal network. A plateau can be seen to the east of the spacecraft, which for the most probable lander location is approximately the direction of a tongue of ejecta from the crater Mie. Boulders at the lander 2 site are generally more vesicular than those near lander i. Fines at both lander sites appear to be very fine-grained and to be bound in a duricrust. The pinkish color of the sky, similar to that observed at the lander I site, indicates suspension of surface material. However, the atmospheric optical depth is less than that at the lander I site. After dissipation of a cloud of dust stirred during landing, no changes other than those stemming from sampling activities have been detected in the landscape. No signs of large organisms are apparent at either landing site.

Fine particles on Mars: observations with the viking 1 lander cameras.

Drifts of fine-grained sediment are present in the vicinity of the Viking 1 lander. Many drifts occur in the lees of large boulders. Morphologic analysis indicates that the last dynamic event was one of general deflation for at least some drifts. Particle cohesion implies that there is a distinct small-particle upturn in the threshold velocity-particle size curve; the apparent absence of the most easily moved particles (150 micrometers in diameter) may be due to their preferential transport to other regions or their preferential collisional destruction. A twilight rescan with lander cameras indicates a substantial amount of red dust with mean radius on the order of 1 micrometer in the atmosphere.

The surface of Mars: there view from the viking 1 lander.

The first photographs ever returned from the surface of Mars were obtained by two facsimile cameras aboard the Viking 1 lander, including black-and-white and color, 0.12 degrees and 0.04 degrees resolution, and monoscopic and stereoscopic images. The surface, on the western slopes of Chtyse Planitia, is a boulder-strewn deeply reddish desert, with distant eminences-some of which may be the rims of impact craters-surmounted by a pink sky. Both impact and aeolian processes are evident. After dissipation of a small dust cloud stirred by the landing maneuvers, no subsequent signs of movement were detected on the landscape, and nothing has been observed that is indicative of macroscopic biology at this time and place.

Mars: the lineament systems.

Analysis of the Mariner 4, Mariner 6, and Mariner 7 photographs shows that Mars has at least two distinct types of lineament systems. The most prominent is a well-developed global-type system. The second consists of radial and concentric lineaments associated with the Hellas and south polar basins.

Martian craters: comparison of statistical counts.

Comparisons of the various crater counts obtained from the Mariner IV photographs indicate that, out of 300 to 600 possible craters mapped by different investigators, only about 120 craters can be reliably identified. Thus, only a lower limit for the Martian crater density can be established from the Mariner IV data.

Mariner IV: Analysis of Preliminary Photographs.

Comparison of the distributions of Martian and lunar crater diameters indicates that the visible surface of Mars is 2.2 to 3 x 10(9) years old. This result implies that in the early history of Mars large-scale subaerial erosion occurred. Of 69 Martian craters with diameters greater than 10 kilometers, 13 percent have central peaks. This compares favorably with the frequency (11.7 percent) of central peaks among lunar craters and may indicate that the central peaks are a direct result of the impact mechanism rather than post-impact volcanism. A well-defined system of lineaments is shown in the Mariner photographs. The presence of these lineaments may indicate that Mars has lost appreciable angular momentum during its history.