Collagens and Cancer associated fibroblasts in the reactive stroma and its relation to Cancer biology

Abstract The extracellular matrix (ECM) plays an important role in cancer progression. It can be divided into the basement membrane (BM) that supports epithelial/endothelial cell behavior and the interstitial matrix (IM) that supports the underlying stromal compartment. The major components of the ECM are the collagens. While breaching of the BM and turnover of e.g. type IV collagen, is a well described part of tumorigenesis, less is known regarding the impact on tumorigenesis from the collagens residing in the stroma. Here we give an introduction and overview to the link between tumorigenesis and stromal collagens, with focus on the fibrillar collagens type I, II, III, V, XI, XXIV and XXVII as well as type VI collagen. Moreover, we discuss the impact of the cells responsible for this altered stromal collagen remodeling, the cancer associated fibroblasts (CAFs), and how these cells are key players in orchestrating the tumor microenvironment composition and tissue microarchitecture, hence also driving tumorigenesis and affecting response to treatment. Lastly, we discuss how specific collagen-derived biomarkers reflecting the turnover of stromal collagens and CAF activity may be used as tools to non-invasively interrogate stromal reactivity in the tumor microenvironment and predict response to treatment

H. C. Andersen og kirkegårdene ude og hjemme

Intet resumé

Young Globular Clusters and Dwarf Spheroidals

Most of the globular clusters in the main body of the Galactic halo were formed almost simultaneously. However, globular cluster formation in dwarf spheroidal galaxies appears to have extended over a significant fraction of a Hubble time. This suggests that the factors which suppressed late-time formation of globulars in the main body of the Galactic halo were not operative in dwarf spheroidal galaxies. Possibly the presence of significant numbers of ``young'' globulars at R_{GC} > 15 kpc can be accounted for by the assumption that many of these objects were formed in Sagittarius-like (but not Fornax-like) dwarf spheroidal galaxies, that were subsequently destroyed by Galactic tidal forces. It would be of interest to search for low-luminosity remnants of parental dwarf spheroidals around the ``young'' globulars Eridanus, Palomar 1, 3, 14, and Terzan 7. Furthermore multi-color photometry could be used to search for the remnants of the super-associations, within which outer halo globular clusters originally formed. Such envelopes are expected to have been tidally stripped from globulars in the inner halo.Comment: 18 pages, with 2 figures, in LaTeX format; to appear in the Astrophysical Journal in February 200

A low upper-limit on the lithium isotope ratio in HD140283

We have obtained a high-S/N (900-1100), high-resolving-power (R=95000) spectrum of the metal-poor subgiant HD 140283 in an effort to measure its 6Li/7Li isotope ratio. From a 1-D atmospheric analysis, we find a value consistent with zero, 6Li/7Li = 0.001, with an upper limit of 6Li/7Li < 0.026. This measurement supersedes an earlier detection (0.040 +/- 0.015(1sigma)) by one of the authors. HD 140283 provides no support for the suggestion that Population II stars may preserve their 6Li on the portion of the subgiant branch where 7Li is preserved. However, this star does not defeat the suggestion either; being at the cool end of subgiant branch of the Spite plateau, it may be sufficiently cool that 6Li depletion has already set in, or the star may be sufficiently metal poor that little Galactic production of 6Li had occurred. Continued investigation of other subgiants is necessary to test the idea. We also consider the implications of the HD 140283 upper limit in conjunction with other measurements for models of 6Li production by cosmic rays from supernovae and structure formation shocks.Comment: 8 pages, 4 figures; accepted for publication in Astronomy and Astrophysic

Tumour burden in early stage Hodgkin's disease: the single most important prognostic factor for outcome after radiotherapy.

One hundred and forty-two patients with Hodgkin's disease PS I or II were treated with total or subtotal nodal irradiation as part of a prospective randomized trial in the Danish National Hodgkin Study during the period 1971-83. They were followed till death or--at the time of this analysis--from 15 to 146 months after initiation of therapy. The initial tumour burden of each patient was assessed, combining tumour size of each involved region and number of regions involved. Tumour burden thus assessed proved to be the single most important prognostic factor with regard to disease free survival. Other known prognostic factors such as number of involved regions, mediastinal size, pathological stage, systemic symptoms, and ESR were related to tumour burden and lost their prognostic significance in a multivariate analysis. The only other factors of independent significance were histologic subtype and, to a lesser extent, sex. Combining tumour burden and histologic subtype made it possible to single out a group of patients with a very poor disease free survival. These patients also had a poorer survival from Hodgkin's disease and thus clearly candidates for additional initial treatment

Kinematics of Nearby Subdwarf Stars

We present an analysis of the space motions of 742 subdwarf stars based on the sample of Carney et al. (1994, CLLA). Hipparcos parallaxes, TYC2+HIP proper motions and Tycho2 proper motions were combined with radial velocities and metallicities from CLLA. The kinematical behavior is discussed in particular in relation to their metallicities. The majority of these sample stars have metal abundances of [Fe/H] >-1 and represent the thick disk population. The halo component, with [Fe/H] <-1.6, is characterized by a low mean rotation velocity and a radially elongated velocity ellipsoid. In the intermediate metallicity range (-1.6 < [Fe/H] <-1), we find a significant number of subdwarfs with disklike kinematics. We interpret this population of stars as a metal-weak thick disk population.Comment: 6 pages, 7 figures, accepted by Astronomy & Astrophysic

The impact of bilinguality and language context on the understanding of epistemic adverbs in health communication: the case of English and Russian

AimTo explore how English epistemic adverbs, as used in health communication, are understood by speakers depending on their first language (L1) and language context.MethodsWe used an online dissimilarity rating task with paired doctors' opinions which differed only with respect to the embedded epistemic adverbs (e.g., This treatment definitely has side effects vs. This treatment possibly has side effects). In order to evaluate the possible effect of one's L1, we compared the ratings of English-speaking monolinguals and Russian-English bilinguals in Australia (Study 1). To evaluate the impact of language context, we compared the ratings of Russian-English bilinguals in Australia and Russia (Study 2). The data were interpreted using classical multidimensional scaling (C-MDS) analysis, complemented by cultural consensus analysis and hierarchical cluster analysis.ResultsThe C-MDS analyses returned statistically acceptable results. Intragroup consensus was evident for all speaker groups. They all clustered the high confidence adverbs (clearly, definitely, and obviously) and the hearsay adverbs (presumably and supposedly) similarly. Effects of L1 were seen: for example, unlike the monolinguals, the Russian bilinguals did not include evidently with the high confidence adverbs (Study 1). An effect of context was also evident: Russian-English bilinguals in Australia most resembled the monolinguals in their understanding of epistemic adverbs. The way Russian-based bilinguals clustered epistemic adverbs reflected a less nuanced understanding (Study 2).ConclusionThe subtle differences in how adverbs of likelihood and doubt are understood in health communication suggest extra care is needed when conveying risk and uncertainty to patients from diverse linguistic and/or cultural backgrounds to ensure mutual understanding and mitigate against miscommunication. The impact of L1 and language context on one's understanding highlights the need to explore more widely how epistemic adverbs are understood by diverse populations and, in doing so, improve healthcare communication practices

The Age Of Globular Clusters In Light Of Hipparcos: Resolving the Age Problem?

We review five independent techniques which are used to set the distance scale to globular clusters, including subdwarf main sequence fitting utilizing the recent Hipparcos parallax catalogue. These data together all indicate that globular clusters are farther away than previously believed, implying a reduction in age estimates. This new distance scale estimate is combined with a detailed numerical Monte Carlo study designed to assess the uncertainty associated with the theoretical age-turnoff luminosity relationship in order to estimate both the absolute age and uncertainty in age of the oldest globular clusters. Our best estimate for the mean age of the oldest globular clusters is now $11.5\pm 1.3$Gyr, with a one-sided, 95% confidence level lower limit of 9.5 Gyr. This represents a systematic shift of over 2 $\sigma$ compared to our earlier estimate, due completely to the new distance scale---which we emphasize is not just due to the Hipparcos data. This now provides a lower limit on the age of the universe which is consistent with either an open universe, or a flat, matter dominated universe (the latter requiring H_0 \le 67 \kmsmpc). Our new study also explicitly quantifies how remaining uncertainties in the distance scale and stellar evolution models translate into uncertainties in the derived globular cluster ages. Simple formulae are provided which can be used to update our age estimate as improved determinations for various quantities become available.Comment: 41 pages, including 10 eps figs, uses aaspp4.sty and flushrt.sty, submitted to Ap.J., revised to incorporate FULL Hipparcos catalogue dat