c myc deregulation is involved in melphalan resistance of multiple myeloma role of pdgf bb

Oncogenes are important regulators of cancer growth and progression and their action may be modulated by proteins of the growth factor family, such as angiogenic cytokines, known to be strongly involved in neoplastic evolution. Reciprocal interactions between oncogenes and angiogenic modulators may represent, in haematological neoplasms, including multiple myeloma (MM), a possible mechanism of drug resistance. The aim of this work is to investigate in vitro and in vivo whether or not c-myc deregulation is involved in the melphalan resistance elicited by myeloma patients and consequently to clarify the role of the angiogenic factor PDGF-BB in modulating c-myc protein expression. Fifty-one MM patients on chemotherapy with melphalan were analyzed for structural alterations of the c-myc gene, c-Myc protein expression, as well as for serum PDGF-BB release. For the in vitro study, two M14-derived established cell clones, differing for the c-Myc protein expression (c-Myc low -expressing or constitutively express..

Non-parametric modeling of the intra-cluster gas using APEX-SZ bolometer imaging data

We demonstrate the usability of mm-wavelength imaging data obtained from the APEX-SZ bolometer array to derive the radial temperature profile of the hot intra-cluster gas out to radius r_500 and beyond. The goal is to study the physical properties of the intra-cluster gas by using a non-parametric de-projection method that is, aside from the assumption of spherical symmetry, free from modeling bias. We use publicly available X-ray imaging data from the XMM-Newton observatory and our Sunyaev-Zel'dovich Effect (SZE) imaging data from the APEX-SZ experiment at 150 GHz to de-project the density and temperature profiles for the relaxed cluster Abell 2204. We derive the gas density, temperature and entropy profiles assuming spherical symmetry, and obtain the total mass profile under the assumption of hydrostatic equilibrium. For comparison with X-ray spectroscopic temperature models, a re-analysis of the recent Chandra observation is done with the latest calibration updates. Using the non-parametric modeling we demonstrate a decrease of gas temperature in the cluster outskirts, and also measure the gas entropy profile. These results are obtained for the first time independently of X-ray spectroscopy, using SZE and X-ray imaging data. The contribution of the SZE systematic uncertainties in measuring T_e at large radii is shown to be small compared to the Chandra systematic spectroscopic errors. The upper limit on M_200 derived from the non-parametric method is consistent with the NFW model prediction from weak lensing analysis.Comment: Replaced with the published version; A&A 519, A29 (2010

Discriminant analysis on small cell lung cancer and non-small cell lung cancer by means of NSE and CYFRA-21.1

A correct diagnosis of small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) is essential both for prognostic and therapeutic reasons. We used discriminant analysis as a method to optimize the discriminant power of serum tumour marker levels for differentiation between SCLC and NSCLC. A panel of serum markers, including neurone specific enolase (NSE), cytokeratin fragment antigen 21.1 (CYFRA-21.1), tissue polypeptide antigen (TPA) and carcinoembryonic antigen (CEA) was obtained in 50 consecutive NSCLC and 17 SCLC. Data were analysed by the BMDP statistical program after logarithmic transformation of marker levels. The variables selected were NSE and CYFRA-21.1. Considered together, they were able to give a 97% rate of correct classification. The formula generated (canonic variable, CV) was validated on a group of seven SCLC and 22 NSCLC patients. Only two errors occurred. We therefore conclude that the canonic variable tested, based on NSE and CYFRA-21.1, provides a good discrimination between the two types of lung cancer. The method is rapid, relatively inexpensive, and based on simple serum tests

Linee guida di prevenzione oncologica - Tabagismo

Linee guida sulla prevenzione oncologica predisposte dal Consiglio sanitario regionale toscano

Endothelin-1 Levels Are Increased in Sera and Lesional Skin Extracts of Psoriatic Patients and Correlate with Disease Severity

Endothelins (ETs), in addition to their systematical activities, exert important functions at the skin level, such as increase of keratinocyte proliferation, neo-angiogenesis and leukocyte chemotaxis, which are among the main characteristics of psoriasis. To assess a possible ET-1 involvement in plaque-type psoriasis, ET-1 determinations were carried out in 15 sera and 8 lesional and non-lesional biopsy skin extracts from psoriatic patients and in 15 sera and 5 biopsy skin extracts from healthy volunteers, sex- and age-matched, using commercially available ELISA kits. A statistical analysis of the results showed that ET-1 levels were increased in sera of psoriatic patients, as compared to normal subjects (p = 0.04). In addition, there was a significant correlation between both serum (r = 0.60, p = 0.02) and lesional skin (r = 0.80, p = 0.03) ET-1 values versus the Psoriasis Area and Severity Index scores. Significant increases of the lesional versus the non-lesional (p = 0.01) and versus the normal (p = 0.04) ET-1 skin extract values were observed, together with a significant correlation between lesional and non-lesional ET-1 skin levels (r = 0.79, p = 0.03). These findings were also confirmed at the mRNA level, using RT-PCR analysis, where increased ET-1 mRNA levels, densitometrically measured, were found in the lesional samples versus non-lesional and normal skin. Since interleukin-8 is involved in psoriasis and shares some biological properties with ET-1, we further evaluated the levels of this cytokine in skin extracts. The behaviour of interleukin-8 paralleled that of ET-1, and a significant correlation between these two molecules was observed in the lesional skin (r = 0.76, p = 0.05). Taken together, these data stress that, as previously described for interleukin-8, ET-1 may be involved in inflammatory processes associated with psoriasis

Strong lensing in the MareNostrum Universe: biases in the cluster lens population

Strong lensing is one of the most direct probes of the mass distribution in the inner regions of galaxy clusters. It can be used to constrain the density profiles and to measure the mass of the lenses. Moreover, the abundance of strong lensing events can be used to constrain the structure formation and the cosmological parameters through the so-called "arc-statistics" approach. However, several issues related to the usage of strong lensing clusters in cosmological applications are still controversial, leading to the suspect that several biases may affect this very peculiar class of objects. With this study we aim at better understanding the properties of galaxy clusters which can potentially act as strong lenses. We do so by investigating the properties of a large sample of galaxy clusters extracted from the N-body/hydrodynamical simulation MareNostrum Universe. We explore the correlation between the cross section for lensing and many properties of clusters, like the mass, the three-dimensional and projected shapes, their concentrations, the X-ray luminosity and the dynamical activity. We find that the probability of strong alignments between the major axes of the lenses and the line of sight is a growing function of the lensing cross section. In projection, the strong lenses appear rounder within R200, but we find that their cores tend to be more elliptical as the lensing cross section increases. We also find that the cluster concentrations estimated from the projected density profiles tend to be biased high. The X-ray luminosity of strong lensing clusters is higher than that of normal lenses of similar mass and redshift. This is particular significant for the least massive lenses. Finally, we find that the strongest lenses generally exhibit an excess of kinetic energy within the virial radius, indicating that they are more dynamically active than usual clusters.Comment: 22 pages, 18 figures, accepted for publication on A&

Reduction of serum IGF-I levels in patients affected with Monoclonal Gammopathies of undetermined significance or Multiple Myeloma. Comparison with bFGF, VEGF and K-ras gene mutation

<p>Abstract</p> <p>Background</p> <p>Serum levels of IGF-I in patients affected with multiple myeloma (MM) have been scarcely studied. The present study is aimed to explore this point comparing 55 healthy subjects, 71 monoclonal gammopaties of uncertain significance (MGUS) and 77 overt MM patients. In the same subjects, basic FGF and VEGF, have been detected. All three mediators were analyzed in function of K-<it>ras </it>mutation and melphalan response. Concerning IGF-I, two representative monitoring examples have also been added.</p> <p>Methods</p> <p>Cytokine determinations were performed by commercially available ELISA kits, while K12-<it>ras </it>mutation was investigated on genomic DNA isolated from bone marrow cell specimens by RFLP-PCR assay.</p> <p>Results</p> <p>Significant reductions of IGF-I levels were observed in MGUS and MM as compared with healthy controls. In addition, MM subjects showed significantly decreased serum IGF-I levels than MGUS. Conversely, increasing levels were observed for bFGF and VEGF, molecules significantly correlated. A multivariate analysis corrected for age and gender confirmed the significant difference only for IGF-I values (P = 0.01). K12-<it>ras </it>mutation was significantly associated with malignancy, response to therapy and with significantly increased serum bFGF levels.</p> <p>Conclusion</p> <p>IGF-I reduction in the transition: Controls→MGUS→MM and changes observed over time suggest that IGF-I should be furtherly studied in future clinical trials as a possible monitoring marker for MM.</p