751 research outputs found

    Concordance of KRAS/BRAF Mutation Status in Metastatic Colorectal Cancer before and after Anti-EGFR Therapy

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    Anti-EGFR targeted therapy is a potent strategy in the treatment of metastatic colorectal cancer (mCRC) but activating mutations in the KRAS gene are associated with poor response to this treatment. Therefore, KRAS mutation analysis is employed in the selection of patients for EGFR-targeted therapy and various studies have shown a high concordance between the mutation status in primary CRC and corresponding metastases. However, although development of therapy related resistance occurs also in the context of novel drugs such as tyrosine kinase-inhibitors the effect of the anti-EGFR treatment on the KRAS/BRAF mutation status itself in recurrent mCRC has not yet been clarified. Therefore, we analyzed 21 mCRCs before/after anti-EGFR therapy and found a pre-/posttherapeutic concordance of the KRAS/BRAF mutation status in 20 of the 21 cases examined. In the one discordant case, further analyses revealed that a tumor mosaicism or multiple primary tumors were present, indicating that anti-EGFR therapy has no influence on KRAS/BRAF mutation status in mCRC. Moreover, as the preselection of patients with a KRASwt genotype for anti-EGFR therapy has become a standard procedure, sample sets such ours might be the basis for future studies addressing the identification of potential anti-EGFR therapy induced genetic alterations apart from KRAS/BRAF mutations

    Investigation of emitter homogeneity on laser doped emitters

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    The selective emitter formation by laser doping is a well known process to increase the efficiency of silicon solar cells [1], [2]. For the characterization of laser doped emitters, SIMS (Secondary Ion Mass Spectroscopy) and ECV (Electrochemical Capacitance Voltage Measurement) techniques are used to analyze the emitter profile [3]. It is very difficult to get acceptable result by SIMS on a textured surface, so only ECV can be used. It has been shown, that a charge carrier depth profile can be measured on a homogeneous emitter only by ECV. The use of laser doping results in a non-homogeneous emitter. We have shown that the emitter depth is not just a function of the pulse power, but in addition of the surface structure of the wafer. The texture seems responsible for a strong variability in the doping profile. It has been shown, that the ECV measurement is not applicable to characterize the emitter depth on laser doped areas, because of the microscopic inhomogeneities in the emitter on the macroscopic measurement area. The real emitter profiles are to complex to be characterized by SIMS or ECV. We have shown that the variation in the emitter profile is resulting from the texture in the laser-doped regions

    Three‐dimensional forward stratigraphic modelling of the sedimentary architecture of meandering‐river successions in evolving half‐graben rift basins

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    The spatial organisation of meandering‐river deposits varies greatly within the sedimentary fills of rift basins, depending on how differential rates of fault propagation and subsidence interplay with autogenic processes to drive changes in fluvial channel‐belt position and rate of migration, avulsion frequency and mechanisms of meander‐bend cut off. This set of processes fundamentally influences stacking patterns of the accumulated successions. Quantitative predictions of the spatio‐temporal evolution and internal architecture of meandering fluvial deposits in such tectonically active settings remain limited. A numerical forward stratigraphic model—the Point‐Bar Sedimentary Architecture Numerical Deduction (PB‐SAND)—is applied to examine relationships between differential rates of subsidence and resultant fluvial channel‐belt migration, reach avulsion and channel‐deposit stacking in active, fault‐bounded half‐grabens. The model is used to reconstruct and predict the complex morphodynamics of fluvial meanders, their generated channel belts, and the associated lithofacies distributions that accumulate as heterogeneous fluvial successions in rift settings, constrained by data from seismic images and outcrop successions. The 3D modelling outputs are used to explore sedimentary heterogeneity at various spatio‐temporal scales. Results show how the connectivity of sand‐prone geobodies can be quantified as a function of subsidence rate, which itself decreases both along and away from the basin‐bounding fault. In particular, results highlight the spatial variability in the size and connectedness of sand‐prone geobodies that is seen in directions perpendicular and parallel to the basin axis, and that arises as a function of the interaction between spatial and temporal variations in rates of accommodation generation and fault‐influenced changes in river morphodynamics. The results have applied significance, for example, to both hydrocarbon exploration and assessment of groundwater aquifers. The expected greatest connectivity of fluvial sandbody in a half‐graben is primarily determined by the complex interplay between the frequency and rate of subsidence, the style of basin propagation, the rates of migration of channel belts, the frequency of avulsion and the proportion and spatial distribution of variably sand‐prone channel and bar deposits

    Effect of conditioning regimen intensity on CMV infection in allogeneic hematopoietic cell transplantation.

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    Nonmyeloablative conditioning is less toxic and results in initial establishment of mixed hematopoietic T cell chimerism for up to half a year with prolonged presence of host T cell immunity. In this study, we examined whether this translates into differences in the risks and/or severity of cytomegalovirus (CMV) infection and disease. We analyzed data from 537 nonmyeloablative (NM-HCT) and contemporaneous 2489 myeloablative hematopoietic cell transplant (M-HCT) recipients. In CMV seropositive recipients, no difference in the overall hazards of CMV infection at any level (adjusted hazard ratio [adj. HR] 0.9, 95% confidence interval [95% CI]: 0.7-1.0, P = .14) was noted; however, NM-HCT was associated with a lower risk of high-grade CMV infection (adj. HR 0.7, 95% CI: 0.5-0.9, P = .02). CMV disease rates were similar between the groups during the first 100 days after HCT, but NM-HCT recipients had an increased risk of late CMV disease (adj. HR 2.0, 95% CI 1.2-3.4). The increased risk of late CMV disease after NM-HCT was pronounced during the earlier years of the study period, but not detectable in more recent years. Contrary to earlier reports, survival following CMV disease was not reduced after NM-HCT when compared to M-HCT recipients. These results suggest that residual host cells after NM-HCT reduce progression to higher CMV viral load in NM-HCT recipients; however, this effect does not appear to protect against serious complications of CMV. Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients

    Chimeric Antigen Receptor T-Cell Therapy For Multiple Myeloma: A Consensus Statement From The European Myeloma Network

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    Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed / refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy is a potentially life-threatening strategy that can only be administered in experienced centers. For the moment, CAR-T cell therapy for MM is still experimental, but once this strategy has been approved in relapsed/refractory MM, it will become one of the most important indications for this therapy in Europe and world-wide. This manuscript proposes practical considerations for the use of CAR-T cell therapy in MM, and discusses several important issues for its future development
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