12 research outputs found

    Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity

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    <p>Abstract</p> <p>Background</p> <p>The prototypical antiprogestin mifepristone exhibits potent growth inhibition activity towards ovarian cancer cells <it>in vitro </it>and <it>in vivo</it>. The aim of this research was to establish whether mifepristone is capable of inhibiting cell proliferation and inducing apoptotic cell death regardless of the degree of sensitivity ovarian cancer cells exhibit to cisplatin.</p> <p>Methods</p> <p>OV2008, OV2008/C13, A2780, A2780/CP70, Caov-3, and SK-OV-3 cell lines exhibiting a range of sensitivities to cisplatin were used. Growth inhibition, cell viability, and sub-diploid DNA content in response to treatment with escalating doses of either mifepristone or cisplatin were assessed by microcapillary cytometry. Apoptotic cell death was evaluated by measuring genomic DNA fragmentation and cleavage of caspase-3 and poly (ADP ribose) polymerase (PARP).</p> <p>Results</p> <p>The sensitivities to cisplatin manifested by the cell lines were OV2008 > A2780 > Caov-3 > SK-OV-3 > OV2008/C13 > A2780/CP70. Mifepristone inhibited the growth of all six cell lines in a dose-related manner with IC<sub>50s </sub>ranging from ~6–12 ÎŒM and without significant correlation with the relative sensitivities the cells displayed for cisplatin. Moreover, at the highest concentration studied, mifepristone triggered apoptotic death in all six cell lines as evidenced by the increase in sub-diploid fragmented DNA content and cleavage of caspase-3 and of its downstream substrate PARP.</p> <p>Conclusion</p> <p>Mifepristone is cytotoxic towards ovarian cancer cells independent of the sensitivity exhibited by the cells to cisplatin, displaying cytostatic effects at lower concentrations and lethal effects at higher concentrations. Mifepristone monotherapy emerges as a valuable therapeutic alternative for platinum-resistant ovarian cancers.</p

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

    Mass-length Relationships for 3 Bee Species in Northwest Ohio

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    The ability to accurately estimate bee mass through measurements of intertegular distance (ITD) is an important tool for field biologists. ITD is the distance between the bases of the 2 wing tegulae on the bee’s thorax. However, the relationship between ITD and bee mass can vary based on species and sampling region. A collection of 92 bees—representing 3 species—was examined to assess the accuracy of ITD in estimating dry mass for bees in northwest Ohio.  The focus was on 3 species: silky striped sweat bees (Agapostemon sericeus), honey bees (Apis mellifera), and common eastern bumble bees (Bombus impatiens).  Overall, there was a positive correlation between ITD and dry mass across all individuals sampled (R2 = 0.77), but within species the degree of correlation varied significantly. The results suggest that ITD accurately estimates dry mass in silky striped sweat bees (R2 = 0.93), but the correlation weakens in common eastern bumble bees (R2 = 0.54) and is non-existent in honey bees (R2 = 0.39). Field biologists interested in using ITD to estimate bee mass should take preliminary measurements when investigating bumble bees, and should avoid ITD estimates in honey bees

    TESS Reveals a Short-period Sub-Neptune Sibling (HD 86226c) to a Known Long-period Giant Planet

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    The Transiting Exoplanet Survey Satellite mission was designed to find transiting planets around bright, nearby stars. Here we present the detection and mass measurement of a small, short-period (≈ 4\approx\,4\,days) transiting planet around the bright (V=7.9V=7.9), solar-type star HD 86226 (TOI-652, TIC 22221375), previously known to host a long-period (∌\sim1600 days) giant planet. HD 86226c (TOI-652.01) has a radius of 2.16±0.082.16\pm0.08 R⊕R_{\oplus} and a mass of 7.25−1.12+1.19^{+1.19}_{-1.12} M⊕M_{\oplus} based on archival and new radial velocity data. We also update the parameters of the longer-period, not-known-to-transit planet, and find it to be less eccentric and less massive than previously reported. The density of the transiting planet is 3.973.97 g cm−3^{-3}, which is low enough to suggest that the planet has at least a small volatile envelope, but the mass fractions of rock, iron, and water are not well-constrained. Given the host star brightness, planet period, and location of the planet near both the ``radius gap'' and the ``hot Neptune desert'', HD 86226c is an interesting candidate for transmission spectroscopy to further refine its composition.Comment: Accepted in AJ on 22 June 202

    TOI-824 b: A New Planet on the Lower Edge of the Hot Neptune Desert

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    We report the detection of a transiting hot Neptune exoplanet orbiting TOI-824 (SCR J1448-5735), a nearby (d = 64 pc) K4V star, using data from the Transiting Exoplanet Survey Satellite. The newly discovered planet has a radius R p = 2.93 ± 0.20 R⊕ and an orbital period of 1.393 days. Radial velocity measurements using the Planet Finder Spectrograph and the High Accuracy Radial velocity Planet Searcher spectrograph confirm the existence of the planet, and we estimate its mass to be 18.47 ± 1.84 M⊕. The planet's mean density is ρp = 4.03-0.78+0.98 g cm-3, making it more than twice as dense as Neptune. TOI-824 b's high equilibrium temperature makes the planet likely to have a cloud-free atmosphere, and thus it is an excellent candidate for follow-up atmospheric studies. The detectability of TOI-824 b's atmosphere from both ground and space is promising and could lead to the detailed characterization of the most irradiated small planet at the edge of the hot Neptune desert that has retained its atmosphere to date
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