The changing face of cancer therapeutics improved : outcome and decreased toxicity with Molecular Targeted Drugs

The treatment of patients with cancer has largely involved the administration of cytotoxic drugs with narrow therapeutic indices, with little selectivity for cancer cells over normal proliferating cells. The primary exception to this has been the successful administration of hormonal manipulation to treat breast and prostate malignancies. The development of hormonal manipulation arose from the observation by Sir George Beatson that breast carcinomas improved after bilateral oophorectomy. This led to the use of Tamoxifen and more recently aromatase inhibitors and oestrogen receptor antagonists. These targeted therapeutics are characterised by their ability to induce selective tumour cell death and achieve patient benefit with low toxicity, and have had a significant impact on the outcome of patients with early and advanced oestrogen receptor positive breast cancer. Further advances in the understanding of tumour cell biology, the sequencing of the human genome, and the characterisation of the molecular differences between malignant and normal cells have, over the past two decades, resulted in the identification of a large number of critically important molecular targets. As with the identification of the importance of oestrogens and the oestrogen receptor, this has accelerated the development of molecularly targeted therapeutics and is rapidly revolutionising cancer medicine (Table 1). This brief review will describe some of the most important advances achieved and will attempt to predict what future cancer therapeutics will entail.peer-reviewe

Period-Color and Amplitude-Color Relations in Classical Cepheid Variables - VI. New Challenges for Pulsation Models

We present multiphase Period-Color/Amplitude-Color/Period-Luminosity relations using OGLE III and Galactic Cepheid data and compare with state of the art theoretical pulsation models. Using this new way to compare models and observations, we find convincing evidence that both Period-Color and Period-Luminosity Relations as a function of phase are dynamic and highly nonlinear at certain pulsation phases. We extend this to a multiphase Wesenheit function and find the same result. Hence our results cannot be due to reddening errors. We present statistical tests and the urls of movies depicting the Period-Color/Period Luminosity and Wesenheit relations as a function of phase for the LMC OGLE III Cepheid data: these tests and movies clearly demonstrate nonlinearity as a function of phase and offer a new window toward a deeper understanding of stellar pulsation. When comparing with models, we find that the models also predict this nonlinearity in both Period-Color and Period-Luminosity planes. The models with (Z=0.004, Y=0.25) fare better in mimicking the LMC Cepheid relations, particularly at longer periods, though the models predict systematically higher amplitudes than the observations

Distance and reddening of the Local Group dwarf irregular galaxy NGC 6822

On the basis of a new photometric analysis of the Local Group dwarf irregular galaxy NCG 6822 based on observations obtained with the Advanced Camera for Surveys onboard the Hubble Space Telescope, we have obtained a new estimate of the extinction of two fields located in the southeast region of the galaxy. Because of significant differences in the distance estimates to NGC 6822 available in literature, we decided to provide an independent determination of the distance to this galaxy based on an updated and self-consistent theoretical calibration of the tip of the red giant branch brightness. As a result we newly determined the distance to NGC 6822 to be equal to ${\rm(m-M)}_0=23.54\pm 0.05$, and compared our measurement with the most recent determinations of this distance.Comment: 5 pages, 5 figures, Astronomy & Astrophysics (Research Note), in press (proof correction included

On the binarity of the classical Cepheid X Sgr from interferometric observations

Optical-infrared interferometry can provide direct geometrical measurements of the radii of Cepheids and/or reveal unknown binary companions of these stars. Such information is of great importance for a proper calibration of Period-Luminosity relations and for determining binary fraction among Cepheids. We observed the Cepheid X Sgr with VLTI/AMBER in order to confirm or disprove the presence of the hypothesized binary companion and to directly measure the mean stellar radius, possibly detecting its variation along the pulsation cycle. From AMBER observations in MR mode we performed a binary model fitting on the closure phase and a limb-darkened model fitting on the visibility. Our analysis indicates the presence of a point-like companion at a separation of 10.7 mas and 5.6 magK fainter than the primary, whose flux and position are sharply constrained by the data. The radius pulsation is not detected, whereas the average limb-darkened diameter results to be 1.48+/-0.08 mas, corresponding to 53+/-3 R_sun at a distance of 333.3 pc.Comment: 5 pages, 3 figures, research not

Synthetic properties of bright metal-poor variables. II. BL Her stars

We investigate the properties of the so-called BL Her stars, i.e., Population II Cepheids with periods shorter than 8 days, using updated pulsation models and evolutionary tracks computed adopting a metal abundance in the range of Z=0.0001 to Z=0.004. We derive the predicted Period-Magnitude (PM) and Period-Wesenheit (PW) relations at the various photometric bands and we show that the slopes of these relations are in good agreement with the slopes determined by observed variables in Galactic globular clusters, independently of the adopted M_V(RR)-[Fe/H] relation to get the cluster RR Lyrae-based distance. Moreover, we show that also the distances provided by the predicted PM and PW relations for BL Her stars agree within the errors with the RR Lyrae based values. The use of the predicted relations with W Vir stars, which are Population II Cepheids with periods longer than 8 days, provides no clear evidence for or against a change in the PM and PW slopes around P~10 days.Comment: 12 pages, 6 figures, 6 tables, accepted for publication in A&A on date 16/05/200

The Hottest Horizontal-Branch Stars in omega Centauri - Late Hot Flasher vs. Helium Enrichment

UV observations of some massive globular clusters uncovered a significant population of very hot stars below the hot end of the horizontal branch (HB), the so-called blue hook stars. This feature might be explained either as results of the late hot flasher scenario where stars experience the helium flash while on the white dwarf cooling curve or by the progeny of the helium-enriched sub-population recently postulated to exist in some clusters. Moderately high resolution spectra of stars at the hot end of the blue HB in omega Cen were analysed for atmospheric parameters and abundances using LTE and Non-LTE model atmospheres. In the temperature range 30,000K to 50,000K we find that 35% of our stars are helium-poor (log(n_He/n_H) < -2), 51% have solar helium abundance within a factor of 3 (-1.5 <= log(n_He/n_H) <= -0.5) and 14% are helium-rich (log(n_He/n_H)> -0.4). We also find carbon enrichment in step with helium enrichment, with a maximum carbon enrichment of 3% by mass. At least 14% of the hottest HB stars in omega Cen show helium abundances well above the highest predictions from the helium enrichment scenario (Y = 0.42 corresponding to log(n_He/n_H) ~ -0.74). In addition, the most helium-rich stars show strong carbon enrichment as predicted by the late hot flasher scenario. We conclude that the helium-rich HB stars in omega Cen cannot be explained solely by the helium-enrichment scenario invoked to explain the blue main sequence. (Abridged)Comment: 4 pages, 3 figures, uses aa.cls (enclosed), accepted as A&A Lette

A state-of-the-art analysis of the dwarf irregular galaxy NGC 6822

We present a detailed photometric study of the dwarf irregular galaxy NGC 6822 aimed at investigating the properties of its stellar populations and, in particular, the presence of stellar radial gradients. Our goal is to analyse the stellar populations in six fields, which cover the whole bar of this dwarf galaxy. We derived the quantitative star formation history (SFH) of the six fields using the IAC method, involving IAC-pop/MinnIAC codes. The solutions we derived show an enhanced star formation rate (SFR) in Fields 1 and 3 during the past 500 Myr. The SFRs of the other fields are almost extinguished at very recent epochs and. We study the radial gradients of the SFR and consider the total mass converted into stars in two time intervals (between 0 and 0.5 Gyr ago and between 0.5 and 13.5 Gyr ago). We find that the scale lengths of the young and intermediate-to-old populations are perfectly compatible, with the exception of the young populations in Fields 1 and 3. The recent SF in these two fields is greater than in the other ones. This might be an indication that in these two fields we are sampling incipient spiral arms. Further evidence and new observations are required to prove this hypothesis. In addition, we derived the age-metallicity relations. As expected, the metallicity increases with time for all of the fields. We do not observe any radial gradient in the metallicity.Comment: 9 pages, 11 figures, Accepted to A&