A Gene Expression Signature of Acquired Chemoresistance to Cisplatin and Fluorouracil Combination Chemotherapy in Gastric Cancer Patients

We initiated a prospective trial to identify transcriptional alterations associated with acquired chemotherapy resistance from pre- and post-biopsy samples from the same patient and uncover potential molecular pathways involved in treatment failure to help guide therapeutic alternatives.A prospective, high-throughput transcriptional profiling study was performed using endoscopic biopsy samples from 123 metastatic gastric cancer patients prior to cisplatin and fluorouracil (CF) combination chemotherapy. 22 patients who initially responded to CF were re-biopsied after they developed resistance to CF. An acquired chemotherapy resistance signature was identified by analyzing the gene expression profiles from the matched pre- and post-CF treated samples. The acquired resistance signature was able to segregate a separate cohort of 101 newly-diagnosed gastric cancer patients according to the time to progression after CF. Hierarchical clustering using a 633-gene acquired resistance signature (feature selection at P<0.01) separated the 101 pretreatment patient samples into two groups with significantly different times to progression (2.5 vs. 4.7 months). This 633-gene signature included the upregulation of AKT1, EIF4B, and RPS6 (mTOR pathway), DNA repair and drug metabolism genes, and was enriched for genes overexpressed in embryonic stem cell signatures. A 72-gene acquired resistance signature (a subset of the 633 gene signature also identified in ES cell-related gene sets) was an independent predictor for time to progression (adjusted P = 0.011) and survival (adjusted P = 0.034) of these 101 patients.This signature may offer new insights into identifying new targets and therapies required to overcome the acquired resistance of gastric cancer to CF

Weak and strong solutions of equations of compressible magnetohydrodynamics

International audienceThis article proposes a review of the analysis of the system of magnetohydrodynamics (MHD). First, we give an account of the modelling asumptions. Then, the results of existence of weak solutions, using the notion of renormalized solutions. Then, existence of strong solutions in the neighbourhood of equilibrium states is reviewed, in particular with the method of Kawashima and Shizuta. Finally, the special case of dimension one is highlighted : the use of Lagrangian coordinates gives a simpler system, which is solved by standard techniques

Computational analysis of expression of human embryonic stem cell-associated signatures in tumors

<p>Abstract</p> <p>Background</p> <p>The cancer stem cell model has been proposed based on the linkage between human embryonic stem cells and human cancer cells. However, the evidences supporting the cancer stem cell model remain to be collected. In this study, we extensively examined the expression of human embryonic stem cell-associated signatures including core genes, transcription factors, pathways and microRNAs in various cancers using the computational biology approach.</p> <p>Results</p> <p>We used the class comparison analysis and survival analysis algorithms to identify differentially expressed genes and their associated transcription factors, pathways and microRNAs among normal vs. tumor or good prognosis vs. poor prognosis phenotypes classes based on numerous human cancer gene expression data. We found that most of the human embryonic stem cell- associated signatures were frequently identified in the analysis, suggesting a strong linkage between human embryonic stem cells and cancer cells.</p> <p>Conclusions</p> <p>The present study revealed the close linkage between the human embryonic stem cell associated gene expression profiles and cancer-associated gene expression profiles, and therefore offered an indirect support for the cancer stem cell theory. However, many interest issues remain to be addressed further.</p

Limits on Anomalous Trilinear Gauge Couplings in Z gamma Events from p(p)over-bar Collisions at root s=1.96 TeV

Using Z gamma candidate events collected by the CDF detector at the Tevatron Collider, we search for potential anomalous (non-standard-model) couplings between the Z boson and the photon. Z gamma couplings vanish at tree level and are heavily suppressed at higher orders; hence any evidence of couplings indicates new physics. Measurements are performed using data corresponding to an integrated luminosity of 4.9 fb(-1) in the Z -> nu(nu) over bar decay channel and 5: 1 fb(-1) in the Z -> l(+)l(-) (l - mu, e) decay channels. The combination of these measurements provides the most stringent limits to date on Z gamma trilinear gauge couplings. Using an energy scale of Lambda = 1.5 TeV to allow for a direct comparison with previous measurements, we find limits on the CP-conserving parameters that describe Z gamma couplings to be vertical bar h(3)(gamma,Z)vertical bar < 0.022 and vertical bar h(4)(gamma,Z)vertical bar < 0.0009. These results are consistent with standard model predictions