The StEllar Counterparts of COmpact high velocity clouds (SECCO) survey. II. Sensitivity of the survey and an Atlas of Synthetic Dwarf Galaxies

SECCO is a survey devoted to the search for stellar counterparts within Ultra Compact High Velocity Clouds. In this contribution we present the results of a set of simulations aimed at the quantitative estimate of the sensitivity of the survey as a function of the total luminosity, size and distance of the stellar systems we are looking for. For all our synthetic galaxies we assumed an exponential surface brightness profile and an old and metal-poor population. The synthetic galaxies are simulated both on the images and on the photometric catalogs, taking into account all the observational effects. In the fields where the available observational material is of the top quality we detect synthetic galaxies as >=5 sigma over-densities of resolved stars down to muV,h=30.0 mag/arcsec2, for D<=1.5 Mpc, and down to muV,h~29.5 mag/arcsec2, for D<=2.5 Mpc. In the field with the worst observational material of the whole survey we detect synthetic galaxies with muV,h<=28.8 mag/arcsec2 out to D<=1.0 Mpc, and those with muV,h<=27.5 mag/arcsec2 out to D<=2.5 Mpc. Dwarf galaxies with MV=-10, with sizes in the range spanned by known dwarfs, are detected by visual inspection of the images up to D=5 Mpc independently of the image quality. In the best quality images dwarfs are partially resolved into stars up to D=3.0 Mpc, and completely unresolved at D=5 Mpc. As an independent test of the sensitivity of our images to low surface brightness galaxies we report on the detection of several dwarf spheroidal galaxies probably located in the Virgo cluster with MV<=-8.0 and muV,h<=26.8 mag/arcsec2. The nature of the previously discovered SECCO 1 stellar system, also likely located in the Virgo cluster, is re-discussed in comparison with these dwarfs. While specific for the SECCO survey, our study may also provide general guidelines for detection of faint stellar systems with 8m class telescopes.Comment: accepted for publication on A&

NGC 5694: another foster son of the Galactic Halo

We present the results of the analysis of high-resolution spectra obtained with UVES-FLAMES@VLT for six red giant branch stars in the outer-halo metal-poor ([Fe/H]I=-1.98 and [Fe/H]II=-1.83) Galactic globular cluster NGC 5694, which has been suggested as a possible incomer by Lee et al. (2006) based on the anomalous chemical composition of a single cluster giant. We obtain accurate abundances for a large number of elements and we find that: (a) the six target stars have the same chemical composition within the uncertainties, except for Na and Al; (b) the average cluster abundance of \alpha\ elements (with the only exception of Si) is nearly solar, at odds with typical halo stars and globular clusters of similar metallicity; (c) Y, Ba, La and Eu abundances are also significantly lower than in Galactic field stars and star clusters of similar metallicity. Hence we confirm the Lee et al. classification of NGC 5694 as a cluster of extra-galactic origin. We provide the first insight on the Na-O and Mg-Al anti-correlations in this cluster: all the considered stars have very similar abundance ratios for these elements, except one that has significantly lower [Na/Fe] and [Al/Fe] ratios, suggesting that some degree of early self-enrichment has occurred also in this cluster.Comment: Accepted for publication by MNRAS. 15 pages, 8 figures, 4 table

THE ROLE OF STEM CELL NICHE AND TUMOR-ASSOCIATED MACROPHAGES IN HUMAN CHOLANGIOCARCINOMA

Background and Aims: Cholangiocarcinoma (CCA) is a highly malignant and extremely heterogeneous adenocarcinoma arising from epithelial cells of bile ducts. CCA is currently associated with poor clinical outcome and, together with hepatocellular carcinoma (HCC), is the major primitive liver cancer in adults. Severity of CCA, lack of good diagnostic markers and frustrating benefit of current therapeutic strategies has rendered this disease a major challenge. Therapeutically challenging subset, termed cancer stem cells (CSCs) has been proposed as a driving force of tumor initiation, dissemination and drug-resistance, including in liver cancer. CSCs could be responsible for CCA wide multi-layered heterogeneity and clinical severity. Although it has already been shown that HCC progression is driven by CSCs, little is known about the presence of CSCs in human CCA. Similar to normal stem cells, CSCs are believed to reside in a specialized microenvironment (\u201cCSC-niche\u201d) within tumor-context that supports self-renewal and drug-resistance. Among various immune-subgroups within CSC-niche, tumor-associated macrophages (TAMs) represent a poor defined but very intriguing immune-subset, whose presence has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may actively shape their tumor-supportive immune niche, specifically CCA-associated macrophages. Methods: CCA cells were cultured in 3D-condition to generate spheres (SPH). CCA-SPH analysis of in vivo tumorigenic-engraftment in immune-deficient mice and molecular characterization was performed as well as evaluation of drug responsiveness. In vitro and in vivo effect of CCA-SPH on macrophage-precursors was tested after culturing healthy donor CD14+ with CCA-SPH conditioned medium (CM). Evaluation of monocyte recruitment as well as macrophage markers\u2019 expression and presence of macrophage functional properties. CCA cells grown in adherence conditions as monolayer (MON) and matched CM used as control. Validation in human specimens. Results: CCA-SPHs engrafted 100% of transplanted mice, revealed a significant 20.3-fold increase in tumor-initiating fraction (p=0.0011) and a sustained tumorigenic potential through diverse xenograft-generations. Moreover, CCA-SPHs were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. CCA-SPH showed also a higher resistance to common chemotherapeutic drugs compared to MON. Analysis of CD14+ chemotaxis revealed that SPH-CM acted as a strong monocyte attractor. Next, fluorescence-activated cell sorting (FACS)-analysis showed that in presence of CCA-SPH-CM, CD14+ expressed key macrophage (M 8) markers (CD68, CD115, HLA-DR, CD206) indicating that CCA-SPH-CM was a strong M 8-activator. Gene expression profile of CCA-SPH activated M 8 (SPH M 8) revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated M 8s from CCA-resections recapitulated similar molecular phenotype of in vitro educated-M 8s. Consistently with invasive features, largest CD163+ set was found in tumor-front of human CCA specimens (n=23) and correlated with high level of serum CA19.9 (n=17). Among mediators released by CCA-SPHs, only IL13, IL34 and Osteoactivin (OA) were detected and further confirmed in CCA patient sera (n=12). Surprisingly, significant association of IL13, IL34 and OA with SPH stem-like genes was provided by CCA database (n=104). In vitro combination of IL13, IL34, OA was responsible for M 8-differentiation and invasion as well as for in vivo tumor-promoting effect. Conclusion: CCA-CSCs molded a specific subset of stem-like associated-M 8s, thus providing a rationale for a synergistic therapeutic strategy for CCA-disease

Kinematics of a globular cluster with an extended profile: NGC5694

We present a study of the kinematics of the remote globular cluster NGC5694 based on GIRAFFE@VLT medium resolution spectra. A sample of 165 individual stars selected to lie on the Red Giant Branch in the cluster Color Magnitude Diagram was considered. Using radial velocity and metallicity from Calcium triplet, we were able to select 83 bona-fide cluster members. The addition of six previously known members leads to a total sample of 89 cluster giants with typical uncertainties <1.0 km/s in their radial velocity estimates. The sample covers a wide range of projected distances from the cluster center, from ~0.2 arcmin to 6.5 arcmin = 23 half-light radii (r_h). We find only very weak rotation, as typical of metal-poor globular clusters. The velocity dispersion gently declines from a central value of sigma=6.1 km/s to sigma = 2.5 km/s at ~2 arcmin = 7.1= r_h, then it remainins flat out to the next (and last) measured point of the dispersion profile, at ~4 arcmin = 14.0 r_h, at odds with the predictions of isotropic King models. We show that both isotropic single-mass non-collisional models and multi-mass anisotropic models can reproduce the observed surface brightness and velocity dispersion profiles.Comment: Accepted for publication by MNRAS. Pdflatex, 10 pages, 10 figure

HST resolves stars in a tiny body falling on the dwarf galaxy DDO 68

We present new Hubble Space Telescope (HST) imaging of a stream-like system associated with the dwarf galaxy DDO 68, located in the Lynx-Cancer Void at a distance of D$\sim$12.65 Mpc from us. The stream, previously identified in deep Large Binocular Telescope images as a diffuse low surface brightness structure, is resolved into individual stars in the F606W (broad V) and F814W ($\sim$I) images acquired with the Wide Field Camera 3. The resulting V, I color-magnitude diagram (CMD) of the resolved stars is dominated by old (age$\gtrsim$1-2 Gyr) red giant branch (RGB) stars. From the observed RGB tip, we conclude that the stream is at the same distance as DDO 68, confirming the physical association with it. A synthetic CMD analysis indicates that the large majority of the star formation activity in the stream occurred at epochs earlier than $\sim$1 Gyr ago, and that the star formation at epochs more recent than $\sim$500 Myr ago is compatible with zero. The total stellar mass of the stream is $\sim10^{6} M_{\odot}$, about 1/100 of that of DDO~68. This is a striking example of hierarchical merging in action at the dwarf galaxy scales.Comment: ApJ in pres

HII regions within a compact high velocity cloud. A nearly star-less dwarf galaxy?

Within the SECCO survey we identified a candidate stellar counterpart to the Ultra Compact High Velocity Cloud (UCHVC) HVC274.68+74.70-123, that was suggested by Adams et al. (2013) as a possible mini-halo within the Local Group of galaxies. The spectroscopic follow-up of the brightest sources within the candidate reveals the presence of two HII regions whose radial velocity is compatible with physical association with the UVHVC. The available data does not allow us to give a definite answer on the nature of the newly identified system. A few alternative hypotheses are discussed. However, the most likely possibility is that we have found a new faint dwarf galaxy residing in the Virgo cluster of galaxies, which we name SECCO-1. Independently of its actual distance, SECCO-1 displays a ratio of neutral hydrogen mass to V luminosity of M_{HI}/L_V>= 20, by far the largest among local dwarfs. Hence, it appears as a nearly star-less galaxy and it may be an example of the missing links between normal dwarfs and the dark mini halos that are predicted to exist in large numbers according to the currently accepted cosmological model.Comment: Accepted for publication in ApJ Letters. Pdflatex, emulateapj.cls. 6 pages, 3 figures, 2 table

Stem-like plasticity and heterogeneity of circulating tumor cells : current status and prospect challenges in liver cancer

Poor prognosis and high recurrence remain leading causes of primary liver cancer-associated mortality. The spread of circulating tumor cells (CTCs) in the blood plays a major role in the initiation of metastasis and tumor recurrence after surgery. Nevertheless, only a subset of CTCs can survive, migrate to distant sites and establish secondary tumors. Consistent with cancer stem cell (CSC) hypothesis, stem-like CTCs might represent a potential source for cancer relapse and distant metastasis. Thus, identification of stem-like metastasis-initiating CTC-subset may provide useful clinically prognostic information. This review will emphasize the most relevant findings of CTCs in the context of stem-like biology associated to liver carcinogenesis. In this view, the emerging field of stem-like CTCs may deliver substantial contribution in liver cancer field in order to move to personalized approaches for diagnosis, prognosis and therapy

Stemness Features in Liver Cancer

Heterogeneity is a cardinal hallmark of cancer, including primary liver cancer (PLC), and occurs at different layers including putative cell-of-origin. Current evidence suggests that within cellular subpopulations in PLC there are stem-like cells, the cancer stem cells (CSCs). The CSC concept has been recently proposed as an explanation of such intra-tumor heterogeneity. According to this model, CSCs are responsible for tumor initiation, recurrence, metastasis as well as drug-resistance. However, although the CSC hypothesis is intriguing and supported by a large number of experimental studies, there are still open questions regarding the origin of putative CSCs. Since chemo-resistance and recurrence represent major issues in PLC treatment, the development of new therapeutic strategies is needed, for which a good understanding of tumor behavior and in particular of CSCs biology is an imperative prerequisite. In this review we summarize the regulatory pathways that support CSC features in PLC. Moreover, we highlight the key features of hepatic CSC, in terms of enhanced drug-resistance, increased metastatic potential and metabolic rearrangement. Knowledge of the molecular mechanisms underlying CSC biology may provide novel options for PLC combination therapies