Cytochrome P17 inhibition with ketoconazole as treatment for advanced granulosa cell ovarian tumor

Originally published by the American Society of Clinical Oncology. García-Donas et al.: Journal of Clinical Oncology Vol. 31.10, April 1 - 2013: e165-e16

The UV-Optical Galaxy Color-Magnitude Diagram. I. Basic Properties

We have analyzed the bivariate distribution of galaxies as a function of ultraviolet-optical colors and absolute magnitudes in the local universe. The sample consists of galaxies with redshifts and optical photometry from the Sloan Digital Sky Survey (SDSS) main galaxy sample matched with detections in the near-ultraviolet (NUV) and far-ultraviolet (FUV) bands in the Medium Imaging Survey being carried out by the Galaxy Evolution Explorer (GALEX) satellite. In the (NUV − r)_(0.1) versus M_(r,0.1) galaxy color-magnitude diagram, the galaxies separate into two well-defined blue and red sequences. The (NUV − r)_(0.1) color distribution at each M_(r,0.1) is not well fit by the sum of two Gaussians due to an excess of galaxies in between the two sequences. The peaks of both sequences become redder with increasing luminosity, with a distinct blue peak visible up to M_(r,0.1) ~ − 23. The r_(0.1)-band luminosity functions vary systematically with color, with the faint-end slope and characteristic luminosity gradually increasing with color. After correcting for attenuation due to dust, we find that approximately one-quarter of the color variation along the blue sequence is due to dust, with the remainder due to star formation history and metallicity. Finally, we present the distribution of galaxies as a function of specific star formation rate and stellar mass. The specific star formation rates imply that galaxies along the blue sequence progress from low-mass galaxies with star formation rates that increase somewhat with time to more massive galaxies with a more or less constant star formation rate. Above a stellar mass of ~10^(10.5) M_☉, galaxies with low ratios of current to past averaged star formation rate begin to dominate

Nitrogen Production in Starburst Galaxies Detected by GALEX

We investigate the production of nitrogen in star-forming galaxies with ultraviolet (UV) radiation detected by the Galaxy Evolution Explorer Satellite (GALEX). We use a sample of 8745 GALEX emission-line galaxies matched to the Sloan Digital Sky Survey (SDSS) spectroscopic sample. We derive both gas-phase oxygen and nitrogen abundances for the sample and apply stellar population synthesis models to derive stellar masses and star formation histories of the galaxies. We compare oxygen abundances derived using three different diagnostics. We derive the specific star formation rates of the galaxies by modeling the seven-band GALEX+SDSS photometry. We find that galaxies that have log (SFR/M_*) ≳ − 10.0 typically have values of log (N/O) ~ 0.05 dex less than galaxies with log (SFR/M_*) ≾ − 10.0 and similar oxygen abundances

The GALEX Ultraviolet Atlas of Nearby Galaxies

We present images, integrated photometry, and surface-brightness and color profiles for a total of 1034 nearby galaxies recently observed by the Galaxy Evolution Explorer (GALEX) satellite in its far-ultraviolet (FUV; λ_(eff) = 1516 Å) and near-ultraviolet (NUV; λ_(eff) = 2267 Å) bands. Our catalog of objects is derived primarily from the GALEX Nearby Galaxies Survey (NGS) supplemented by galaxies larger than 1' in diameter serendipitously found in these fields and in other GALEX exposures of similar of greater depth. The sample analyzed here adequately describes the distribution and full range of properties (luminosity, color, star formation rate [SFR]) of galaxies in the local universe. From the surface brightness profiles obtained we have computed asymptotic magnitudes, colors, and luminosities, along with the concentration indices C31 and C42. We have also morphologically classified the UV surface brightness profiles according to their shape. This data set has been complemented with archival optical, near-infrared, and far-infrared fluxes and colors. We find that the integrated (FUV − K) color provides robust discrimination between elliptical and spiral/irregular galaxies and also among spiral galaxies of different subtypes. Elliptical galaxies with brighter K-band luminosities (i.e., more massive) are redder in (NUV − K) color but bluer in (FUV − NUV) (a color sensitive to the presence of a strong UV upturn) than less massive ellipticals. In the case of the spiral/irregular galaxies our analysis shows the presence of a relatively tight correlation between the (FUV − NUV) color (or, equivalently, the slope of the UV spectrum, β) and the total infrared-to-UV ratio. The correlation found between (FUV − NUV) color and K-band luminosity (with lower luminosity objects being bluer than more luminous ones) can be explained as due to an increase in the dust content with galaxy luminosity. The images in this Atlas along with the profiles and integrated properties are publicly available through a dedicated Web page

Experience with Sunitinib in metastatic renal cell carcinoma (mRCC) patients: pooled analysis from 3 Spanish observational prospective studies

[Abstract] Background: A pivotal, randomized, phase III trial demonstrated a statistically significant superiority of sunitinib over interferon-α in metastatic renal cell carcinoma (mRCC) patients. Objective: To evaluate the effectiveness and safety of sunitinib in patients with advanced or mRCC in routine clinical practice. Methods: Retrospective pooled analysis of clinical data from three observational and prospective studies carried out between 2007 and 2011 in 33 Spanish hospitals. Tumor response, Progression-free survival (PFS) and overall survival (OS), and main sunitinib-related toxicities were registered. Results: 224 patients were analyzed. Median PFS 10.6 months (95% CI: 9.02–12.25), median OS 21.9 months (95% CI: 17.2–26.6). Objective response rate (ORR) 43.8% (95% CI: 36.8–50.7). Median time to PR was 3.8 months (95% CI: 3.86–5.99) and to CR 8.2 months (95% CI: 4.75–9.77). The most common ≥ grade-3 AEs were asthenia/fatigue (18.7%), hand-foot syndrome (6.2%), hypertension (5.8%) and neutropenia (4.8%). Hand-foot syndrome, diarrhea and mucositis were confirmed as independent predictors for PFS and/or OS in a multivariate analysis (p < 0.05) Conclusions: Outcomes with sunitinib in daily clinical practice resemble those obtained in clinical trials. Long-term benefit with sunitinib is possible in advanced RCC patients but the appropriate management of toxicities is mandatory to enable patients to remain on treatment

The NER-related gene GTF2H5 predicts survival in high-grade serous ovarian cancer patients

We aimed to evaluate the prognostic and predictive value of the nucleotide excision repair-related gene GTF2H5, which is localized at the 6q24.2-26 deletion previously reported by our group to predict longer survival of high-grade serous ovarian cancer patients. In order to test if protein levels of GTF2H5 are associated with patients' outcome, we performed GTF2H5 immunohistochemical staining in 139 high-grade serous ovarian carcinomas included in tissue microarrays. Upon stratification of cases into high- and low-GTF2H5 staining categories (> and ≤ median staining, respectively) Kaplan-Meier and log-rank test were used to estimate patients' survival and assess statistical differences. We also evaluated the association of GTF2H5 with survival at the transcriptional level by using the on-line Kaplan-Meier plotter tool, which includes gene expression and survival data of 855 high-grade serous ovarian cancer patients from 13 different datasets. Finally, we determined whether stable short hairpin RNA-mediated GTF2H5 downregulation modulates cisplatin sensitivity in the SKOV3 and COV504 cell lines by using cytotoxicity assays. Low expression of GTF2H5 was associated with longer 5-year survival of patients at the protein (hazard ratio [HR], 0.52; 95% CI, 0.29 to 0.93; p=0.024) and transcriptional level (HR, 0.80; 95% CI, 0.65 to 0.97; p=0.023) in high-grade serous ovarian cancer patients. We confirmed the association with 5-year overall survival (HR, 0.55; 95% CI, 0.38 to 0.78; p=0.0007) and also found an association with progression-free survival (HR, 0.72; 95% CI, 0.54 to 0.96; p=0.026) in a homogenous group of 388 high-stage (stages III-IV using the International Federation of Gynecology and Obstetrics staging system), optimally debulked high-grade serous ovarian cancer patients. GTF2H5- silencing induced a decrease of the half maximal inhibitory concentration upon cisplatin treatment in GTF2H5 -silenced ovarian cancer cells. Low levels of GTF2H5 are associated with enhanced prognosis in high-grade serous ovarian cancer patients and may contribute to cisplatin sensitization

The Extreme Hosts of Extreme Supernovae

We use GALEX ultraviolet (UV) and optical integrated photometry of the hosts of seventeen luminous supernovae (LSNe, having peak M_V < -21) and compare them to a sample of 26,000 galaxies from a cross-match between the SDSS DR4 spectral catalog and GALEX interim release 1.1. We place the LSNe hosts on the galaxy NUV-r versus M_r color magnitude diagram (CMD) with the larger sample to illustrate how extreme they are. The LSN hosts appear to favor low-density regions of the galaxy CMD falling on the blue edge of the blue cloud toward the low luminosity end. From the UV-optical photometry, we estimate the star formation history of the LSN hosts. The hosts have moderately low star formation rates (SFRs) and low stellar masses (M_*) resulting in high specific star formation rates (sSFR). Compared with the larger sample, the LSN hosts occupy low-density regions of a diagram plotting sSFR versus M_* in the area having higher sSFR and lower M_*. This preference for low M_*, high sSFR hosts implies the LSNe are produced by an effect having to do with their local environment. The correlation of mass with metallicity suggests that perhaps wind-driven mass loss is the factor that prevents LSNe from arising in higher-mass, higher-metallicity hosts. The massive progenitors of the LSNe (>100 M_sun), by appearing in low-SFR hosts, are potential tests for theories of the initial mass function that limit the maximum mass of a star based on the SFR.Comment: 8 pages, 3 figures, 2 tables, accepted to ApJ, amended references and updated SN designation

The Star Formation Law at Low Surface Density

We investigate the nature of the star formation law at low gas surface densities using a sample of 19 low surface brightness (LSB) galaxies with existing H I maps in the literature, UV imaging from the Galaxy Evolution Explorer satellite, and optical images from the Sloan Digital Sky Survey. All of the LSB galaxies have (NUV – r) colors similar to those for higher surface brightness star-forming galaxies of similar luminosity indicating that their average star formation histories are not very different. Based upon four LSB galaxies with both UV and far-infrared (FIR) data, we find FIR/UV ratios significantly less than 1, implying low amounts of internal UV extinction in LSB galaxies. We use the UV images and H I maps to measure the star formation rate (SFR) and hydrogen gas surface density within the same region for all the galaxies. The LSB galaxy star formation rate surface densities lie below the extrapolation of the power law fit to the SFR surface density as a function of the total gas density for higher surface brightness galaxies. Although there is more scatter, the LSB galaxies also lie below a second version of the star formation law in which the SFR surface density is correlated with the gas density divided by the orbital time in the disk. The downturn seen in both star formation laws is consistent with theoretical models that predict lower star formation efficiencies in LSB galaxies due to the declining molecular fraction with decreasing density

Chemical and Photometric Evolution of Extended Ultraviolet Disks: Optical Spectroscopy of M83 (NGC 5236) and NGC 4625

We present the results from the analysis of optical spectra of 31 Hα-selected regions in the extended UV (XUV) disks of M83 (NGC 5236) and NGC 4625 recently discovered by GALEX. The spectra were obtained using IMACS at the Las Campanas Observatory 6.5 m Magellan I telescope and COSMIC at the Palomar 200 inch (5 m) telescope, respectively, for M83 and NGC 4625. The line ratios measured indicate nebular oxygen abundances (derived from the R23 parameter) of the order of Z_⊙/5-Z_⊙/10. For most emission-line regions analyzed the line fluxes and ratios measured are best reproduced by models of photoionization by single stars with masses in the range 20-40 M_⊙ and oxygen abundances comparable to those derived from the R23 parameter. We find indications for a relatively high N/O abundance ratio in the XUV disk of M83. Although the metallicities derived imply that these are not the first stars formed in the XUV disks, such a level of enrichment could be reached in young spiral disks only 1 Gyr after these first stars would have formed. The amount of gas in the XUV disks allows maintaining the current level of star formation for at least a few Gyr