Endothelial progenitor cell-breast cancer interaction

Breast cancer remains the second leading cause of cancer death among women in the U.S. Although organ-confined disease is curable, metastatic disease remains incurable and an unmet clinical need. Hence, the development of new therapeutic targets and further understanding of the genesis of malignant progression is needed and to this end analysis of the tumor microenvironment is imperative for novel therapeutic targets in breast cancer. We and others have demonstrated that bone marrow derived endothelial progenitor cells (EPCs) incorporate in the neovasculature around implanted tumors supporting their growth and metastasis. The incorporation of EPCs from the marrow to the tumor is estrogen responsive. We evaluated the effect of estrogen and a naturally occurring anti-estrogen 3, 3’-diindolylmethane (DIM) on precursor progenitor cells of angiogenesis, EPCs, at the cellular and molecular levels using CD133+ /CD34+ stem cells that were isolated by positive selection from human umbilical cord blood as an in vitro model of vasculogenesis. Moreover, we evaluated the secretome of the EPCs and their role in breast cancer progression. Using flow cytometry, we show that the highly proliferative EPCs can differentiate into functional endothelial cells. We concluded that EPCs are estrogen sensitive, and estradiol mediated enhancement of the function of EPCs is abrogated by the anti-estrogen DIM. We further elucidated the significance and function of EPCs in the breast cancer environment using in vitro models and attempted to define the interacting determinants. We examined the cell-cell interaction by evaluating the effect of conditioned media from EPCs on breast cancer cell and vice versa. We further isolated secretory exosomes from EPCs and breast cancer and examined their mutual interaction using end point measurements such as cell proliferation, invasion, and migration. Further, we xviii examined the contents of the exosomes in term of their microRNAs, and the cytokines in the tumor microenvironment. We report that exosomes of EPCs are enriched with oncogenic miRNAs including hsa-miR-16-5p, hsa-miR-17-5p, hsa-miR-181a-5p, hsa-miR-21-5p, hsa-miR-142-3p, and their miRNAs are also significant modulators of breast cancer transformation and metastasis. Our studies are consistent with the hypothesis that secretory exosomes and paracrine cytokines are shuttles of cell-cell communication and important targets of novel breast cancer therapy. The exosomes and the microRNAs they carry are the communicating determinants between breast cancer cells and EPCs in the tumor microenvironment and presumably help evolution of breast cancer subsets such as the triple negative breast cancer (TNBC) with gain of metastatic phenotype. Disruption of the cell-cell communication can lead to novel TNBC therapeutic and fulfill a much-needed clinical need

Pilonidal sinus: why does it recur

Introduction: Ring formation, a structural chromosomal abnormality, is frequently observed in X chromosome. This article reports the 45,X along with 46,X, r(X) cell lines and its associations to the observed phenotypic features in an Indian female proband aged 15 years. Methods: The karyotype was determined from peripheral lymphocyte culture and Giemsa-Trypsin banding technique. Results: The karyotype was 45,X/46,X,r(X) (p11q13) (18%82%). The presence of 45,X and ring X in mosaicism status indicates that the karyotype is a Turner syndrome variant. The variably manifested phenotypic features in the proband could be due to the presence of single X, the lost segments in ring X and the mosaicism status for the X. Conclusion: During counseling, proband’s chromosomal status and its effect were explained to the proband’s parents. Parents were also counselled about the importance of medical management, education and career to the proband

Color Portion of Solar Radiation in the Partial Annular Solar Eclipse, October 3rd, 2005, at Helwan, Egypt

Measurements were made of various solar radiation components, global, direct and diffuse and their fractions during the partial annular solar eclipse on October 3rd, 2005 at Helwan, Egypt (Lat. 29.866◦ N and Long. 31.20◦ E), and an analysis has been made. The duration of the solar eclipse was 3 h 17 min, and the maximum magnitude of the eclipse in this region was 0.65. The optical depth of the direct component and the relative humidity decreased, while both the transparency and the air temperature increased towards the maximum eclipse. The general trends of the global components are decreasing optical depth and increasing transparency between the first contact and the last contact. The prevailing color during the eclipse duration was diffused infrared (77 % of the total diffuse radiation level)

NAKED EYE ESTIMATES OF MORNING PRAYER AT TUBRUQ OF LIBYA

Naked eye observations at Tubruq sky (φ = 32° 05´, λ = 23° 59´) in Libya at the Mediterranean coast (see-desert background) during the two years (2008 – 2009) of morning twilight have been recorded.  These observations led us to get some estimates about morning twilight, as it is necessary to determine the time of the True Dawn (Al-Fajr Prayer Time).  this research aims to determine the correct time of Al-Fajr Prayer by finding the accurate angle of the sun vertical depression below the horizon that is associated with legitimate mark. The Methode used in this research was field research while the observations have been recorded by monitoring the first white thread on the eastern horizon (True Dawn) that announces the time of the Morning Prayer (Al-Fajr Prayer).  The azimuthally range of observation about the solar vertical extends from 0° up to ±20°, while the phenomenon was followed from 0° up to 20° along the altitudinal range.  This research gives a result that a beginning of the morning twilight is estimated to be around 13.5° depression of the sun below the horizon.  This value can reach a minimum depression around 11.5° at low visibility and a maximum around 13.5° at a very god visibility

NAKED EYE ESTIMATES OF MORNING PRAYER AT TUBRUQ OF LIBYA

Naked eye observations at Tubruq sky (φ = 32° 05´, λ = 23° 59´) in Libya at the Mediterranean coast (see-desert background) during the two years (2008 – 2009) of morning twilight have been recorded.  These observations led us to get some estimates about morning twilight, as it is necessary to determine the time of the True Dawn (Al-Fajr Prayer Time).  this research aims to determine the correct time of Al-Fajr Prayer by finding the accurate angle of the sun vertical depression below the horizon that is associated with legitimate mark. The Methode used in this research was field research while the observations have been recorded by monitoring the first white thread on the eastern horizon (True Dawn) that announces the time of the Morning Prayer (Al-Fajr Prayer).  The azimuthally range of observation about the solar vertical extends from 0° up to ±20°, while the phenomenon was followed from 0° up to 20° along the altitudinal range.  This research gives a result that a beginning of the morning twilight is estimated to be around 13.5° depression of the sun below the horizon.  This value can reach a minimum depression around 11.5° at low visibility and a maximum around 13.5° at a very god visibility

Macrophage Inflammatory Factors Promote Epithelial-Mesenchymal Transition in Breast Cancer

The majority of breast cancers (90-95%) arise due to mediators distinct from inherited genetic mutations. One major mediator of breast cancer involves chronic inflammation. M1 macrophages are an integral component of chronic inflammation and the breast cancer tumor microenvironment (TME). Previous studies have demonstrated that up to 50% of the breast tumor comprise of tumor-associated macrophages (TAMs) and increased TAM infiltration has been associated with poor patient prognosis. Furthermore, breast cancer associated deaths are predominantly attributed to invasive cancers and metastasis with epithelial-mesenchymal transition (EMT) being implicated. In this study, we investigated the effects of cellular crosstalk between TAMs and breast cancer using an in vitro model system. M1 polarized THP-1 macrophage conditioned media (CM) was generated and used to evaluate cellular and functional changes of breast cancer lines T47D and MCF-7. We observed that T47D and MCF-7 exhibited a partial EMT phenotype in the presence of activated THP-1 CM. Additionally, MCF-7 displayed a significant increase in migratory and invasive properties. We conclude that M1 secretory factors can promote a partial EMT of epithelial-like breast cancer cells. The targeting of M1 macrophages or their secretory components may inhibit EMT and limit the invasive potential of breast cancer

Influence of artificial aging and ZrO2 nanoparticle-reinforced repair resin on the denture repair strength

Background: The purpose of this study was to evaluate the effect of aging process on the tensile strength (TS) of repaired acrylic denture base using ZrO2 nanoparticles (nano-ZrO2)-reinforced autopolymerized resin. Material and Methods: A total of 240 heat-polymerized acrylic resin specimens (n=10) were prepared and sectioned creating 2 mm-repair-gap. Autopolymerized acrylic resin, pure and modified with 2.5, 5, and 7.5wt% nano-ZrO2were used for specimens repair. TS of repaired specimens were measured using the universal testing machine af-ter water immersion at 37oC for 2, 7 and 30 days. At each time interval, half the immersed specimens underwent thermo-cycling aging process (5000 cycles at 5/55°C) before TS testing. One-way ANOVA and Tukey-Kramer multiple-comparison tests were used for data analysis at ?=0.05. Results: Aging process for all groups showed significant differences in TS between unreinforced and nano-ZrO2reinforced groups (p<0.05). Within immersed nano-ZrO2-reinforced specimens, 5% group immersed for 30-days showed the highest significant TS value (p<0.05). With regards to thermocycling, 5% group showed the highest TS values after 2-days and 30-days groups while after 7-days, significant differences were found between 2.5% group and 5% and 7.5% groups (p?0.05). SEM images analysis displayed the ductile fracture type for nano-ZrO2reinforced groups.Conclusions: In summary, 5.0%-nano-ZrO2 addition to repair resin showed an improvement in tensile strength of repaired acrylic resin with different aging processes

Orbital effects of non-isotropic mass depletion of the atmospheres of evaporating hot Jupiters in extrasolar systems

We analytically and numerically investigate the long-term, i.e. averaged over one full revolution, orbital effects of the non-isotropic percent mass loss \dot m/m experienced by several transiting hot Jupiters whose atmospheres are hit by severe radiations flows coming from their close parent stars. The semi-major axis a, the argument of pericenter \omega and the mean anomaly M experience net variations, while the eccentricity e, the inclination I and the longitude of the ascending node remain unchanged, on average. In particular, a increases independently of e and of the speed Vesc of the ejected mass. By assuming |\dot m| <= 10^17 kg yr-1, corresponding to |\dot m/m| <= 10^-10 yr-1 for a Jupiter-like planet, it turns out \dot a = 2.5 m yr^-1 for orbits with a = 0.05 au. Such an effect may play a role in the dynamical history of the hot Jupiters, especially in connection with the still unresolved issue of the arrest of the planetary inward migrations after a distance a >= 0.01 au is reached. The retrograde pericenter variation depends, instead, on e and V_esc. It may, in principle, act as a source of systematic uncertainty in some proposed measurements of the general relativistic pericenter precession; however, it turns out to be smaller than it by several orders of magnitude.Comment: LaTex2e, 16 pages, no tables, 6 figures. To appear in New Astronomy (NA

Orbital Separation Amplification in Fragile Binaries with Evolved Components

The secular stellar mass-loss causes an amplification of the orbital separation in fragile, common proper motion, binary systems with separations of the order of 1000 A.U. In these systems, companions evolve as two independent coeval stars as they experience negligible mutual tidal interactions or mass transfer. We present models for how post-main sequence mass-loss statistically distorts the frequency distribution of separations in fragile binaries. These models demonstrate the expected increase in orbital seapration resulting from stellar mass-loss, as well as a perturbation of associated orbital parameters. Comparisons between our models and observations resulting from the Luyten survey of wide visual binaries, specifically those containing MS and white-dwarf pairs, demonstrate a good agreement between the calculated and the observed angular separation distribution functions.Comment: 37 pages, 13 figure