Expression of the apoptotic markers in normal breast epithelium, benign mammary dysplasia and in breast cancer

Apoptosis and proliferation are processes associated with the development and progression of breast cancer. The sensitivity of tumour cells to the induction of apoptosis depends on the balance between pro- and anti-apoptotic proteins. The expression of Bak and Bcl-2 was examined using an immunohistochemical method in 71 primary breast cancers. Furthermore, Bcl-2 and Bak were assessed in the normal mammary gland as well as in benign mammary dysplasia adjacent to breast cancer. Positive immunostaining for Bcl-2 was observed in 77.8% of cases of normal breast epithelium (NBE), 93% of benign dysplasia without intraductal proliferation (BBD) as well as in 94% of intraductal proliferative lesions of the breast (BIPL). Expression of Bak was detected in 39% of cases of NBE, 45% of BBD and in 67% of BIPL. In breast cancer Bcl-2 and Bak expression was found in 83% and 70% of the cases studied, respectively. Increased Bcl-2 expression in primary tumours significantly correlated with favourable prognostic factors, namely pT1, G2 and lack of metastases to the regional lymph nodes (p < 0.01, p < 0.03, p < 0.02, respectively). There were no relationships between Bak and the clinicopathological features studied, but our results indicate changes in the expression of Bak during breast cancer development and progression. It would appear to be important to assess and compare pro- and anti-apoptotic proteins between normal mammary gland, benign mammary dysplasia and the primary tumours of breast cancer. This knowledge should be helpful in understanding breast cancer development and progression

Increased expression of leptin and the leptin receptor as a marker of breast cancer progression: possible role of obesity-related stimuli

PURPOSE: Recent in vitro studies suggested that the autocrine leptin loop might contribute to breast cancer development by enhancing cell growth and survival. To evaluate whether the leptin system could become a target in breast cancer therapy, we examined the expression of leptin and its receptor (ObR) in primary and metastatic breast cancer and noncancer mammary epithelium. We also studied whether the expression of leptin/ObR in breast cancer can be induced by obesity-related stimuli, such as elevated levels of insulin, insulin-like growth factor-I (IGF-I), estradiol, or hypoxic conditions. EXPERIMENTAL DESIGN: The expression of leptin and ObR was examined by immunohistochemistry in 148 primary breast cancers and 66 breast cancer metastases as well as in 90 benign mammary lesions. The effects of insulin, IGF-I, estradiol, and hypoxia on leptin and ObR mRNA expression were assessed by reverse transcription-PCR in MCF-7 and MDA-MB-231 breast cancer cell lines. RESULTS: Leptin and ObR were significantly overexpressed in primary and metastatic breast cancer relative to noncancer tissues. In primary tumors, leptin positively correlated with ObR, and both biomarkers were most abundant in G3 tumors. The expression of leptin mRNA was enhanced by insulin and hypoxia in MCF-7 and MDA-MB-231 cells, whereas IGF-I and estradiol stimulated leptin mRNA only in MCF-7 cells. ObR mRNA was induced by insulin, IGF-I, and estradiol in MCF-7 cells and by insulin and hypoxia in MDA-MB-231 cells. CONCLUSIONS: Leptin and ObR are overexpressed in breast cancer, possibly due to hypoxia and/or overexposure of cells to insulin, IGF-I, and/or estradiol

Towards understanding the relation between the gas and the attenuation in galaxies at kpc scales

[abridged] Aims. The aim of the present paper is to provide new and more detailed relations at the kpc scale between the gas surface density and the face-on optical depth directly calibrated on galaxies, in order to compute the attenuation not only for semi-analytic models but also observationally as new and upcoming radio observatories are able to trace gas ever farther in the Universe. Methods. We have selected a sample of 4 nearby resolved galaxies and a sample of 27 unresolved galaxies from the Herschel Reference Survey and the Very Nearby Galaxies Survey, for which we have a large set of multi-wavelength data from the FUV to the FIR including metallicity gradients for resolved galaxies, along with radio HI and CO observations. For each pixel in resolved galaxies and for each galaxy in the unresolved sample, we compute the face-on optical depth from the attenuation determined with the CIGALE SED fitting code and an assumed geometry. We determine the gas surface density from HI and CO observations with a metallicity-dependent XCO factor. Results. We provide new, simple to use, relations to determine the face-on optical depth from the gas surface density, taking the metallicity into account, which proves to be crucial for a proper estimate. The method used to determine the gas surface density or the face-on optical depth has little impact on the relations except for galaxies that have an inclination over 50d. Finally, we provide detailed instructions on how to compute the attenuation practically from the gas surface density taking into account possible information on the metallicity. Conclusions. Examination of the influence of these new relations on simulated FUV and IR luminosity functions shows a clear impact compared to older oft-used relations, which in turn could affect the conclusions drawn from studies based on large scale cosmological simulations.Comment: 24 pages, 21 figures, accepted for publication in A&

Tidal disruption of dark matter halos around proto-globular clusters

Tidal disruption of dark matter halos around proto-globular clusters in a halo of a small galaxy is studied in the context of the hierarchical clustering scenario by using semi-cosmological N-body/SPH simulations assuming the standard cold dark matter model ($\Omega_0 = 1$). Our analysis on formation and evolution of the galaxy and its substructures archives until $z = 2.0$. In such a high-redshift universe, the Einstein-de Sitter universe is still a good approximation for a recently favored $\Lambda$-dominated universe, and then our results does not depend on the choice of cosmology. In order to resolve small gravitationally-bound clumps around galaxies and consider radiative cooling below $T = 10^4 K$, we adopt a fine mass resolution (m_{\rm SPH} = 1.12 \times 10^3 \Msun). Because of the cooling, each clump immediately forms a `core-halo' structure which consists of a baryonic core and a dark matter halo. The tidal force from the host galaxy mainly strips the dark matter halo from clumps and, as a result, theses clumps get dominated by baryons. Once a clump is captured by the host halo, its mass drastically decreases each pericenter passage. At $z = 2$, more than half of the clumps become baryon dominated systems (baryon mass/total mass $> 0.5$). Our results support the tidal evolution scenario of the formation of globular clusters and baryon dominated dwarf galaxies in the context of the cold dark matter universe.Comment: 9page, 13 figures. Accepted for publication in ApJ. A high-resolution PDF of the paper can be obtained from http://th.nao.ac.jp/~takayuki/ApJ05

The properties of the Malin 1 galaxy giant disk: A panchromatic view from the NGVS and GUViCS surveys

Low surface brightness galaxies (LSBGs) represent a significant percentage of local galaxies but their formation and evolution remain elusive. They may hold crucial information for our understanding of many key issues (i.e., census of baryonic and dark matter, star formation in the low density regime, mass function). The most massive examples - the so called giant LSBGs - can be as massive as the Milky Way, but with this mass being distributed in a much larger disk. Malin 1 is an iconic giant LSBG, perhaps the largest disk galaxy known. We attempt to bring new insights on its structure and evolution on the basis of new images covering a wide range in wavelength. We have computed surface brightness profiles (and average surface brightnesses in 16 regions of interest), in six photometric bands (FUV, NUV, u, g, i, z). We compared these data to various models, testing a variety of assumptions concerning the formation and evolution of Malin 1. We find that the surface brightness and color profiles can be reproduced by a long and quiet star-formation history due to the low surface density; no significant event, such as a collision, is necessary. Such quiet star formation across the giant disk is obtained in a disk model calibrated for the Milky Way, but with an angular momentum approximately 20 times larger. Signs of small variations of the star-formation history are indicated by the diversity of ages found when different regions within the galaxy are intercompared.For the first time, panchromatic images of Malin 1 are used to constrain the stellar populations and the history of this iconic example among giant LSBGs. Based on our model, the extreme disk of Malin 1 is found to have a long history of relatively low star formation (about 2 Msun/yr). Our model allows us to make predictions on its stellar mass and metallicity.Comment: Accepted in Astronomy and Astrophysic

Youngsters do not pay attention to conversational rules: is this so for nonhuman primates?

The potentiality to find precursors of human language in nonhuman primates is questioned because of differences related to the genetic determinism of human and nonhuman primate acoustic structures. Limiting the debate to production and acoustic plasticity might have led to underestimating parallels between human and nonhuman primates. Adult-young differences concerning vocal usage have been reported in various primate species. A key feature of language is the ability to converse, respecting turn-taking rules. Turn-taking structures some nonhuman primates' adult vocal exchanges, but the development and the cognitive relevancy of this rule have never been investigated in monkeys. Our observations of Campbell's monkeys' spontaneous vocal utterances revealed that juveniles broke the turn-taking rule more often than did experienced adults. Only adults displayed different levels of interest when hearing playbacks of vocal exchanges respecting or not the turn-taking rule. This study strengthens parallels between human conversations and nonhuman primate vocal exchanges

Relationships between hypoxia markers and the leptin system, estrogen receptors in human primary and metastatic breast cancer: effects of preoperative chemotherapy

<p>Abstract</p> <p>Background</p> <p>Tumor hypoxia is marked by enhanced expression of hypoxia-inducible factor-α (HIF-1α) and glucose transporter-1 (Glut-1). Hypoxic conditions have also been associated with overexpression of angiogenic factors, such as leptin. The aim of our study was to analyze the relationships between hypoxia markers HIF-1α, Glut-1, leptin, leptin receptor (ObR) and other breast cancer biomarkers in primary and metastatic breast cancer in patients treated or untreated with preoperative chemotherapy.</p> <p>Methods</p> <p>The expression of different biomarkers was examined by immunohistochemistry in 116 primary breast cancers and 65 lymph node metastases. Forty five of these samples were obtained form patients who received preoperative chemotherapy and 71 from untreated patients.</p> <p>Results</p> <p>In primary tumors without preoperative chemotherapy, HIF-1α and Glut-1 were positively correlated (p = 0.02, r = 0.437). HIF-1α in primary and metastatic tumors without preoperative therapy positively correlated with leptin (p < 0.0001, r = 0.532; p = 0.013, r = 0.533, respectively) and ObR (p = 0.002, r = 0.319; p = 0.083, r = 0.387, respectively). Hypoxia markers HIF-1α and Glut-1 were negatively associated with estrogen receptor alpha (ERα) and positively correlated with estrogen receptor beta (ERβ). In this group of tumors, a positive correlation between Glut-1 and proliferation marker Ki-67 (p = 0.017, r = 0.433) was noted. The associations between HIF-1α and Glut-1, HIF-1α and leptin, HIF-1α and ERα as well as Glut-1 and ERβ were lost following preoperative chemotherapy.</p> <p>Conclusions</p> <p>Intratumoral hypoxia in breast cancer is marked by coordinated expression of such markers as HIF-1α, Glut-1, leptin and ObR. The relationships among these proteins can be altered by preoperative chemotherapy.</p

Enhanced stability of layered phases in parallel hard-spherocylinders due to the addition of hard spheres

There is increasing evidence that entropy can induce microphase separation in binary fluid mixtures interacting through hard particle potentials. One such phase consists of alternating two dimensional liquid-like layers of rods and spheres. We study the transition from a uniform miscible state to this ordered state using computer simulations and compare results to experiments and theory. We conclude that (1) there is stable entropy driven microphase separation in mixtures of parallel rods and spheres, (2) adding spheres smaller then the rod length decreases the total volume fraction needed for the formation of a layered phase, therefore small spheres effectively stabilize the layered phase; the opposite is true for large spheres and (3) the degree of this stabilization increases with increasing rod length.Comment: 11 pages, 9 figures. Submitted to Phys. Rev. E. See related website http://www.elsie.brandeis.ed

A Resolved Ring of Debris Dust around the Solar Analog HD 107146

We present resolved images of the dust continuum emission from the debris disk around the young (80-200 Myr) solar-type star HD 107146 with CARMA at λ = 1.3 mm and the CSO at λ = 350 μ. Both images show that the dust emission extends over an approximately 10" diameter region. The high-resolution (3") CARMA image further reveals that the dust is distributed in a partial ring with significant decrease in a flux inward of 97 AU. Two prominent emission peaks appear within the ring separated by ~140° in the position angle. The morphology of the dust emission is suggestive of dust captured into a mean motion resonance, which would imply the presence of a planet at an orbital radius of ~45-75 AU