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- Houshmand, M, et al.
(author)
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Targeting Chronic Myeloid Leukemia Stem/Progenitor Cells Using Venetoclax-Loaded Immunoliposome
- 2021
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In: Cancers. - : MDPI AG. - 2072-6694. ; 13:6
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Journal article (peer-reviewed)abstract
- CML is a hematopoietic stem-cell disorder emanating from breakpoint cluster region/Abelson murine leukemia 1 (BCR/ABL) translocation. Introduction of different TKIs revolutionized treatment outcome in CML patients, but CML LSCs seem insensitive to TKIs and are detectable in newly diagnosed and resistant CML patients and in patients who discontinued therapy. It has been reported that CML LSCs aberrantly express some CD markers such as CD26 that can be used for the diagnosis and for targeting. In this study, we confirmed the presence of CD26+ CML LSCs in newly diagnosed and resistant CML patients. To selectively target CML LSCs/progenitor cells that express CD26 and to spare normal HSCs/progenitor cells, we designed a venetoclax-loaded immunoliposome (IL-VX). Our results showed that by using this system we could selectively target CD26+ cells while sparing CD26− cells. The efficiency of venetoclax in targeting CML LSCs has been reported and our system demonstrated a higher potency in cell death induction in comparison to free venetoclax. Meanwhile, treatment of patient samples with IL-VX significantly reduced CD26+ cells in both stem cells and progenitor cells population. In conclusion, this approach showed that selective elimination of CD26+ CML LSCs/progenitor cells can be obtained in vitro, which might allow in vivo reduction of side effects and attainment of treatment-free, long-lasting remission in CML patients.
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| 2. |
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| 3. |
- Kakkad, D., et al.
(author)
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SUPER: II. Spatially resolved ionised gas kinematics and scaling relations in z 2 ∼ AGN host galaxies
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 642
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Journal article (peer-reviewed)abstract
- Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) aims to trace and characterise ionised gas outflows and their impact on star formation in a statistical sample of X-ray selected active galactic nuclei (AGN) at z ∼ 2. We present the first SINFONI results for a sample of 21 Type 1 AGN spanning a wide range in bolometric luminosity (log Lbol = 45.4-47.9 erg s-1). The main aims of this paper are to determine the extension of the ionised gas, characterise the occurrence of AGN-driven outflows, and link the properties of such outflows with those of the AGN. Methods. We used adaptive optics-assisted SINFONI observations to trace ionised gas in the extended narrow line region using the [O» III] λ5007 line. We classified a target as hosting an outflow if its non-parametric velocity of the [O» III] line, w80, was larger than 600 km s-1. We studied the presence of extended emission using dedicated point-spread function (PSF) observations, after modelling the PSF from the Balmer lines originating from the broad line region. Results. We detect outflows in all the Type 1 AGN sample based on the w80 value from the integrated spectrum, which is in the range ∼650-2700 km s-1. There is a clear positive correlation between w80 and the AGN bolometric luminosity (> 99% correlation probability), and the black hole mass (98% correlation probability). A comparison of the PSF and the [O» III] radial profile shows that the [O» III] emission is spatially resolved for ∼35% of the Type 1 sample and the outflows show an extension up to ∼6 kpc. The relation between maximum velocity and the bolometric luminosity is consistent with model predictions for shocks from an AGN-driven outflow. The escape fraction of the outflowing gas increases with the AGN luminosity, although for most galaxies, this fraction is less than 10%.
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| 5. |
- Vietri, G., et al.
(author)
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SUPER - III. Broad line region properties of AGNs at z ∼ 2
- 2020
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In: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 644
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Journal article (peer-reviewed)abstract
- Aims. The SINFONI survey for Unveiling the Physics and Effect of Radiative feedback (SUPER) was designed to conduct a blind search for AGN-driven outflows on X-ray-selected AGNs at redshift z similar to 2 with high (similar to 2 kpc) spatial resolution, and to correlate them with the properties of their host galaxy and central black hole. The main aims of this paper are: (a) to derive reliable estimates for the masses of the black holes and accretion rates for the Type-1 AGNs in this survey; and (b) to characterise the properties of the AGN-driven winds in the broad line region (BLR).Methods. We analysed rest-frame optical and UV spectra of 21 Type-1 AGNs. We used H alpha, H beta, and MgII line profiles to estimate the masses of the black holes. We used the blueshift of the CIV line profile to trace the presence of winds in the BLR.Results. We find that the H alpha and H beta line widths are strongly correlated, as is the line continuum luminosity at 5100 angstrom with H alpha line luminosity, resulting in a well-defined correlation between black hole masses estimated from H alpha and H beta. Using these lines, we estimate that the black hole masses for our objects are in the range Log (M-BH/M-circle dot) = 8.4-10.8 and are accreting at lambda (Edd) = 0.04-1.3. Furthermore, we confirm the well-known finding that the CIV line width does not correlate with the Balmer lines and the peak of the line profile is blueshifted with respect to the [OIII]-based systemic redshift. These findings support the idea that the CIV line is tracing outflowing gas in the BLR for which we estimated velocities up to similar to 4700 km s(-1). We confirm the strong dependence of the BLR wind velocity on the UV-to-X-ray continuum slope, the bolometric luminosity, and Eddington ratio. We infer BLR mass outflow rates in the range 0.005-3 M-circle dot yr(-1), revealing a correlation with the bolometric luminosity consistent with that observed for ionised winds in the narrow line region (NLR), and X-ray winds detected in local AGNs, and kinetic power similar to 10(-7)-10(-4)xL(Bol). The coupling efficiencies predicted by AGN-feedback models are much higher than the values reported for the BLR winds in the SUPER sample; although it should be noted that only a fraction of the energy injected by the AGN into the surrounding medium is expected to become kinetic power in the outflow. Finally, we find an anti-correlation between the equivalent width of the [OIII] line and the CIV velocity shift, and a positive correlation between this latter parameter and [OIII] outflow velocity. These findings, for the first time in an unbiased sample of AGNs at z similar to 2, support a scenario where BLR winds are connected to galaxy-scale detected outflows, and are therefore capable of affecting the gas in the NLR located at kiloparsec scale distances.
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