Cancer cells grown in 3D under fluid flow exhibit an aggressive phenotype and reduced responsiveness to the anti-cancer treatment doxorubicin.

3D laboratory models of cancer are designed to recapitulate the biochemical and biophysical characteristics of the tumour microenvironment and aim to enable studies of cancer, and new therapeutic modalities, in a physiologically-relevant manner. We have developed an in vitro 3D model comprising a central high-density mass of breast cancer cells surrounded by collagen type-1 and we incorporated fluid flow and pressure. We noted significant changes in cancer cell behaviour using this system. MDA-MB231 and SKBR3 breast cancer cells grown in 3D downregulated the proliferative marker Ki67 (P<0.05) and exhibited decreased response to the chemotherapeutic agent doxorubicin (DOX) (P<0.01). Mesenchymal markers snail and MMP14 were upregulated in cancer cells maintained in 3D (P<0.001), cadherin-11 was downregulated (P<0.001) and HER2 increased (P<0.05). Cells maintained in 3D under fluid flow exhibited a further reduction in response to DOX (P<0.05); HER2 and Ki67 levels were also attenuated. Fluid flow and pressure was associated with reduced cell viability and decreased expression levels of vimentin. In summary, aggressive cancer cell behaviour and reduced drug responsiveness was observed when breast cancer cells were maintained in 3D under fluid flow and pressure. These observations are relevant for future developments of 3D in vitro cancer models and organ-on-a-chip initiatives

Searching for an EBL attenuation signature in the Fermi/LAT 1st year catalog data

Observations of distant sources of high-energy (HE) gamma-rays are affected by attenuation resulting from the interaction of the gamma-rays with low energy photons from the diffuse meta-galactic radiation fields at ultraviolet (UV) to infrared (IR) wavelengths (Extragalactic Background Light; EBL). Recently, a large data-set of HE observations from the 1st year survey of the Large Area Telescope (LAT) instrument on-board of the Fermi satellite became available, covering an energy range from 100 MeV up to 100 GeV. In this paper, the potential of such large HE data-sets to probe the density of the EBL - especially in the UV to optical - is explored. The data from the catalog is investigated for an attenuation signature in the energy range 10-100 GeV and the results are compared with the predictions from EBL model calculations. No clear signature is found. The statistics are still limited by (1) the sensitivity of Fermi/LAT to detect sources above 10 GeV, (2) the number of firmly identified sources with known redshift, both which will improve over the coming years.Comment: 4 pages, 3 figures, accepted for publication in A&A (submitted May 3, 2010

The Evolution of Dust in the Early Universe with Applications to the Galaxy SDSS J1148+5251

Dusty hyperluminous galaxies in the early universe provide unique environments for studying the role of massive stars in the formation and destruction of dust. At redshifts above ~ 6, when the universe was less than ~ 1 Gyr old, dust could have only condensed in the explosive ejecta of Type II supernovae (SNe), since most of the progenitors of the AGB stars, the major alternative source of interstellar dust, did not have time to evolve off the main sequence since the onset of star formation. In this paper we present analytical models for the evolution of the gas, dust, and metals in high redshift galaxies, with a special application to SDSS J1148+5251, a hyperluminous quasar at z = 6.4. We find that an average supernova must condense at least 1 Msun of dust to account for the observed dust mass in this quasar. Observationally, it is in excess of the largest dust yield of ~0.02 Msun found thus far in the ejecta of any SN. If future observations find this to be a typical supernova dust yield, then additional processes, such as accretion onto preexisting grains, or condensation around the AGN will need to be invoked to account for the large amount of dust in this and similar objects. The galaxy's star formation history is still uncertain, and current observations of the gas, metal, and dust contents of J1148 can be reproduced by either an intensive and short burst of star formation (~ 1000 Msun/yr) with a duration of ~ 100 Myr, or a much lower star formation rate (~ 100 Msun/yr) occurring over the lifetime of the galaxy.Comment: 35 pages, 11 figures, accepted for publication in the Astrophysical Journa

Analytical Approximations for Calculating the Escape and Absorption of Radiation in Clumpy Dusty Environments

We present analytical approximations for calculating the scattering, absorption and escape of nonionizing photons from a spherically symmetric two-phase clumpy medium, with either a central point source of isotropic radiation, a uniform distribution of isotropic emitters, or uniformly illuminated by external sources. The analytical approximations are based on the mega-grains model of two-phase clumpy media, as proposed by Hobson & Padman, combined with escape and absorption probability formulae for homogeneous media. The accuracy of the approximations is examined by comparison with 3D Monte Carlo simulations of radiative transfer, including multiple scattering. Our studies show that the combined mega-grains and escape/absorption probability formulae provide a good approximation of the escaping and absorbed radiation fractions for a wide range of parameters characterizing the medium. A realistic test is performed by modeling the absorption of a starlike source of radiation by interstellar dust in a clumpy medium, and by calculating the resulting equilibrium dust temperatures and infrared emission spectrum of both the clumps and the interclump medium. In particular, we find that the temperature of dust in clumps is lower than in the interclump medium if clumps are optically thick. Comparison with Monte Carlo simulations of radiative transfer in the same environment shows that the analytic model yields a good approximation of dust temperatures and the emerging UV to FIR spectrum of radiation for all three types of source distributions mentioned above. Our analytical model provides a numerically expedient way to estimate radiative transfer in a variety of interstellar conditions and can be applied to a wide range of astrophysical environments, from star forming regions to starburst galaxies.Comment: 55 pages, 27 figures. ApJ 523 (1999), in press. Corrected equations and text so as to be same as ApJ versio

The large scale gas and dust distribution in the galaxy: Implications for star formation

Infrared Astronomy Observations are presented for the diffuse infrared (IR) emissions from the galactic plane at wavelengths of 60 and 100 microns and the total far infrared intensity and its longitudinal variations in the disk were derived. Using available CO, 5 GHz radio-continuum, and HI data, the IR luminosity per hydrogen mass and the ingrared excess (IRE) ratio in the Galaxy were derived. The longitudinal profiles of the 60 and 100 micron emission were linearly decomposed into three components that are associated with molecular (H2), neutral (HI), and ionized (HII) phases in the interstellar medium (ISM), and the relevant dust properties were derived in each phase. Implications of the findings for various models of the diffuse IR emisison and for star formation in the galactic disk are discussed

Cadherin-5: a biomarker for metastatic breast cancer with optimum efficacy in oestrogen receptor-positive breast cancers with vascular invasion

Background: A glycoproteomic study has previously shown cadherin-5 (CDH5) to be a serological marker of metastatic breast cancer when both protein levels and glycosylation status were assessed. In this study we aimed to further validate the utility of CDH5 as a biomarker for breast cancer progression. Methods: A nested case–control study of serum samples from breast cancer patients, of which n=52 had developed a distant metastatic recurrence within 5 years post-diagnosis and n=60 had remained recurrence-free. ELISAs were used to quantify patient serum CDH5 levels and assess glycosylation by Helix pomatia agglutinin (HPA) binding. Clinicopathological, treatment and lifestyle factors associated with metastasis and elevated biomarker levels were identified. Results: Elevated CDH5 levels (P=0.028) and ratios of CDH5:HPA binding (P=0.007) distinguished patients with metastatic disease from those that remained metastasis-free. Multivariate analysis showed that the association between CDH5:HPA ratio and the formation of distant metastases was driven by patients with oestrogen receptor (ER+) positive cancer with vascular invasion (VI+). Conclusions: CDH5 levels and the CDH5 glycosylation represent biomarker tests that distinguish patients with metastatic breast cancer from those that remain metastasis-free. The test reached optimal sensitivity and specificity in ER-positive cancers with vascular invasion

Conjugation of quantum dots on carbon nanotubes for medical diagnosis and treatment

Cancer is one of the leading causes of death worldwide and early detection provides the best possible prognosis for cancer patients. Nanotechnology is the branch of engineering that deals with the manipulation of individual atoms and molecules. This area of science has the potential to help identify cancerous cells and to destroy them by various methods such as drug delivery or thermal treatment of cancer. Carbon nanotubes (CNT) and quantum dots (QDs) are the two nanoparticles, which have received considerable interest in view of their application for diagnosis and treatment of cancer. Fluorescent nanoparticles known as QDs are gaining momentum as imaging molecules with life science and clinical applications. Clinically they can be used for localization of cancer cells due to their nano size and ability to penetrate individual cancer cells and high-resolution imaging derived from their narrow emission bands compared with organic dyes. CNTs are of interest to the medical community due to their unique properties such as the ability to deliver drugs to a site of action or convert optical energy into thermal energy. By attaching antibodies that bind specifically to tumor cells, CNTs can navigate to malignant tumors. Once at the tumor site, the CNTs enter into the cancer cells by penetration or endocytosis, allowing drug release, and resulting in specific cancer cell death. Alternatively, CNTs can be exposed to near-infrared light in order to thermally destroy the cancer cells. The amphiphilic nature of CNTs allows them to penetrate the cell membrane and their large surface area (in the order of 2600 m2/g) allows drugs to be loaded into the tube and released once inside the cancer cell. Many research laboratories, including our own, are investigating the conjugation of QDs to CNTs to allow localization of the cancer cells in the patient, by imaging with QDs, and subsequent cell killing, via drug release or thermal treatment. This is an area of huge interest and future research and therapy will focus on the multimodality of nanoparticles. In this review, we seek to explore the biomedical applications of QDs conjugated to CNTs, with a particular emphasis on their use as therapeutic platforms in oncology

Functionalization of single-walled carbon nanotubes and their binding to cancer cells

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On the source of the late-time infrared luminosity of SN 1998S and other type II supernovae

We present late-time near-infrared (NIR) and optical observations of the type IIn SN 1998S. The NIR photometry spans 333-1242 days after explosion, while the NIR and optical spectra cover 333-1191 days and 305-1093 days respectively. The NIR photometry extends to the M'-band (4.7 mu), making SN 1998S only the second ever supernova for which such a long IR wavelength has been detected. The shape and evolution of the H alpha and HeI 1.083 mu line profiles indicate a powerful interaction with a progenitor wind, as well as providing evidence of dust condensation within the ejecta. The latest optical spectrum suggests that the wind had been flowing for at least 430 years. The intensity and rise of the HK continuum towards longer wavelengths together with the relatively bright L' and M' magnitudes shows that the NIR emission was due to hot dust newly-formed in supernovae may provide the ejecta and/or pre-existing dust in the progenitor circumstellar medium (CSM). [ABRIDGED] Possible origins for the NIR emission are considered. Significant radioactive heating of ejecta dust is ruled out, as is shock/X-ray-precursor heating of CSM dust. More plausible sources are (a) an IR-echo from CSM dust driven by the UV/optical peak luminosity, and (b) emission from newly-condensed dust which formed within a cool, dense shell produced by the ejecta shock/CSM interaction. We argue that the evidence favours the condensing dust hypothesis, although an IR-echo is not ruled out. Within the condensing-dust scenario, the IR luminosity indicates the presence of at least 0.001 solar masses of dust in the ejecta, and probably considerably more. Finally, we show that the late-time intrinsic (K-L') evolution of type II supernovae may provide a useful tool for determining the presence or absence of a massive CSM around their progenitor stars.Comment: 23 pages, 15 figures, to be published in MNRA

PhytoCloud: A gamified Mobile Web Application to modulate diet and physical activity of women with breast cancer

Breast cancer incidence and mortality rates vary geographically reflecting factors including regional and cultural differences in diet and lifestyle. There are numerous successful commercial mobile apps to help people control their diet and manage weight. However, such products are not suitable for people with special medical conditions that may require targeted dietary as well as motivational support. The paper presents a user centered approach of developing a Mobile Web App that focuses on breast cancer patients looking at their specific dietary, physical and mental requirements depending on the stage of their medical treatment. The paper explores the effect of incorporating gamification and social media as motivational drive to engage and motivate people to achieve their goals of adopting healthier eating habits while increasing physical activity in order ensure lasting lifestyle behavioural change. The design of “PhytoCloud” is being described, a gamified Mobile Web App that enables users to record their dietary habits and physical activity and motivate their consumption of food with oestrogen-like properties (phytoestrogens) which are linked to the prevention of reappearance of breast cancer. The paper concludes with a discussion of future directions and adaptations to the current design to suite a Mobile Native Application design