97 research outputs found
Cyclin D1, cyclin E, and p21 have no apparent prognostic value in anal carcinomas treated by radiotherapy with or without chemotherapy
The purpose of this study was to assess the potential prognostic and/or predictive value of the expression of cyclin D1, cyclin E, and p21 protein in a series of 98 anal carcinomas (T1-4, N0-3) treated by radiotherapy with (51) or without (47) chemotherapy in one institution. Correlation with Mib1 index and p53 expression was also investigated. Median follow-up for surviving patients was 124 months (range: 30-266). Immunohistochemical staining was performed on pretreatment biopsies, applying a standard ABC technique for cyclin D1 (clone DSC6, DAKO, 1 : 300), cyclin E (clone 13A3, Novocastra, 1 : 100), p21(WAF/CIP1) (clone SX118, DAKO, 1 : 50), p53 (clone DO7, DAKO, 1 : 200), and Mib1 (Ki-67, Dianova, 1 : 20). Tumours were classified into low- or high-expression groups according to the expression level of the protein considered. High expression was found in 51% of tumours for cyclin E, in 33.7% for cyclin D1, and in 65% for p21. None of those factors were significantly associated with clinical variables such as advanced T or N categories. In a monovariate analysis, advanced T and N categories and longer overall treatment time were the only variables that correlated significantly with low rate of local control (LC) and disease-free survival. However, in a subgroup analysis, high p21 expression correlated with a trend for significantly higher 5-year LC (87 vs 68%, P=0.07) in the N0 patients. The results of this study suggest that the cell-cycle proteins investigated are unlikely to be clinically useful in predicting treatment response or prognosis in patients with anal carcinomas
Comparison of Hepatic-like Cell Production from Human Embryonic Stem Cells and Adult Liver Progenitor Cells: CAR Transduction Activates a Battery of Detoxification Genes
In vitro production of human hepatocytes is of primary importance in basic research, pharmacotoxicology and biotherapy of liver diseases. We have developed a protocol of differentiation of human embryonic stem cells (ES) towards hepatocyte-like cells (ES-Hep). Using a set of human adult markers including CAAT/enhancer binding protein (C/EBPalpha), hepatocyte nuclear factor 4/7 ratio (HNF4alpha1/HNF4alpha7), cytochrome P450 7A1 (CYP7A1), CYP3A4 and constitutive androstane receptor (CAR), and fetal markers including alpha-fetoprotein, CYP3A7 and glutathione S-transferase P1, we analyzed the expression of a panel of 41 genes in ES-Hep comparatively with human adult primary hepatocytes, adult and fetal liver. The data revealed that after 21Â days of differentiation, ES-Hep are representative of fetal hepatocytes at less than 20Â weeks of gestation. The glucocorticoid receptor pathway was functional in ES-Hep. Extending protocols of differentiation to 4Â weeks did not improve cell maturation. When compared with hepatocyte-like cells derived from adult liver non parenchymal epithelial (NPE) cells (NPE-Hep), ES-Hep expressed several adult and fetal liver makers at much greater levels (at least one order of magnitude), consistent with greater expression of liver-enriched transcription factors Forkhead box A2, C/EBPalpha, HNF4alpha and HNF6. It therefore seems that ES-Hep reach a better level of differentiation than NPE-Hep and that these cells use different lineage pathways towards the hepatic phenotype. Finally we showed that lentivirus-mediated expression of xenoreceptor CAR in ES-Hep induced the expression of several detoxification genes including CYP2B6, CYP2C9, CYP3A4, UDP-glycosyltransferase 1A1, solute carriers 21A6, as well as biotransformation of midazolam, a CYP3A4-specific substrate
OSS (Outer Solar System): A fundamental and planetary physics mission to Neptune, Triton and the Kuiper Belt
The present OSS mission continues a long and bright tradition by associating
the communities of fundamental physics and planetary sciences in a single
mission with ambitious goals in both domains. OSS is an M-class mission to
explore the Neptune system almost half a century after flyby of the Voyager 2
spacecraft. Several discoveries were made by Voyager 2, including the Great
Dark Spot (which has now disappeared) and Triton's geysers. Voyager 2 revealed
the dynamics of Neptune's atmosphere and found four rings and evidence of ring
arcs above Neptune. Benefiting from a greatly improved instrumentation, it will
result in a striking advance in the study of the farthest planet of the Solar
System. Furthermore, OSS will provide a unique opportunity to visit a selected
Kuiper Belt object subsequent to the passage of the Neptunian system. It will
consolidate the hypothesis of the origin of Triton as a KBO captured by
Neptune, and improve our knowledge on the formation of the Solar system. The
probe will embark instruments allowing precise tracking of the probe during
cruise. It allows to perform the best controlled experiment for testing, in
deep space, the General Relativity, on which is based all the models of Solar
system formation. OSS is proposed as an international cooperation between ESA
and NASA, giving the capability for ESA to launch an M-class mission towards
the farthest planet of the Solar system, and to a Kuiper Belt object. The
proposed mission profile would allow to deliver a 500 kg class spacecraft. The
design of the probe is mainly constrained by the deep space gravity test in
order to minimise the perturbation of the accelerometer measurement.Comment: 43 pages, 10 figures, Accepted to Experimental Astronomy, Special
Issue Cosmic Vision. Revision according to reviewers comment
Liver cell therapy: is this the end of the beginning?
The prevalence of liver diseases is increasing globally. Orthotopic liver transplantation is widely used to treat liver disease upon organ failure. The complexity of this procedure and finite numbers of healthy organ donors have prompted research into alternative therapeutic options to treat liver disease. This includes the transplantation of liver cells to promote regeneration. While successful, the routine supply of good quality human liver cells is limited. Therefore, renewable and scalable sources of these cells are sought. Liver progenitor and pluripotent stem cells offer potential cell sources that could be used clinically. This review discusses recent approaches in liver cell transplantation and requirements to improve the process, with the ultimate goal being efficient organ regeneration. We also discuss the potential off-target effects of cell-based therapies, and the advantages and drawbacks of current pre-clinical animal models used to study organ senescence, repopulation and regeneration
Varying constants, Gravitation and Cosmology
Fundamental constants are a cornerstone of our physical laws. Any constant
varying in space and/or time would reflect the existence of an almost massless
field that couples to matter. This will induce a violation of the universality
of free fall. It is thus of utmost importance for our understanding of gravity
and of the domain of validity of general relativity to test for their
constancy. We thus detail the relations between the constants, the tests of the
local position invariance and of the universality of free fall. We then review
the main experimental and observational constraints that have been obtained
from atomic clocks, the Oklo phenomenon, Solar system observations, meteorites
dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic
microwave background and big bang nucleosynthesis. At each step we describe the
basics of each system, its dependence with respect to the constants, the known
systematic effects and the most recent constraints that have been obtained. We
then describe the main theoretical frameworks in which the low-energy constants
may actually be varying and we focus on the unification mechanisms and the
relations between the variation of different constants. To finish, we discuss
the more speculative possibility of understanding their numerical values and
the apparent fine-tuning that they confront us with.Comment: 145 pages, 10 figures, Review for Living Reviews in Relativit
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