17 research outputs found
Nanoparticle-aided glycovariant assays to bridge biomarker performance and ctDNA results
AbstractNumerous immunoassay based cancer
biomarkers established in the 1970 and 1980'ies are widely used in
clinical routine. Initial expectations of biomarkers such as CEA, CA125,
CA19-9, AFP to provide decisive help in the diagnosis of early stage,
pre-symptomatic cancers have not been realized. Thus, they are primarily
used for monitoring disease progression and occasionally being useful
as prognostic indicators. This limitation is due to the marker also
being measurable in healthy individuals and frequently at elevated
concentrations in common benign conditions. Most conventional tumor
markers are glycosylated and interestingly specific alterations of the
glycostructure part can often be seen early in the cancerous process.
Conventional double monoclonal immunoassays are however blind to such
changes as they are based on peptide epitope recognition. Wide
selections of carbohydrate recognizing macromolecules, lectins, but also
glycan structure recognizing antibodies are potentially useful for
detecting such changes. Despite numerous attempts generating
proof-of-principle evidence for this, such assays have generally not
been successfully introduced into clinical routine. The affinity
constants of lectin and glycan specific antibodies for their
corresponding carbohydrate structures may be up to several orders too
low to provide the detection limits and robustness expected from routine
tumor markers. In this review, we describe an approach based on the use
of highly fluorescent Eu3+--chelate dyed nanoparticles onto
which lectins or glycan specific antibodies are coated to provide the
necessary binding strength and signal amplification to provide low
detection limits, while maintaining the original glycan-structure
specificity. This concept applied to three markers, PSA, CA125 and
CA15-3 provide glycoform assays of greatly enhanced cancer specificity
using sample volumes similar or lower than corresponding traditional
ELISAs. For ovarian cancer, we show that this new approach when applied
to ovarian cyst fluid samples provide results similar to the performance
obtained with ctDNA determinations of a set of 17 driver mutations and
greatly superior compared to corresponding conventional immunoassays.
Based on our results, we predict that the nanoparticle-lectin concept
will enable a new generation of simple, low-cost biomarker assays of
highly improved cancer specificity. Such tools should ideally be
evaluated together with determination of ctDNA to establish early
detection schemes for cancers e.g. ovarian, pancreas, lung where the
detection rate of early stage disease is presently unacceptably low.</div
A randomized phase II study of stem cell mobilization with cyclophosphamide plus G-CSF or G-CSF alone after lenalidomide-based induction in multiple myeloma
The most common means of mobilizing autologous stem cells is G-CSF alone or combined with cyclophosphamide (CY) to obtain sufficient CD34(+) cells for one to two transplants. There are few prospective, randomized studies investigating mobilization regimens in multiple myeloma (MM), especially after lenalidomide-based induction. We designed this prospective, randomized study to compare low-dose CY 2 g/m(2)+G-CSF (arm A) and G-CSF alone (arm B) after lenalidomide-based up-front induction in MM. Of the 80 initially randomized patients, 69 patients were evaluable, 34 and 35 patients in arms A and B, respectively. The primary end point was the proportion of patients achieving a yield of >= 3x10(6)/kg CD34(+) cells with 1 - 2 aphereses, which was achieved in 94% and 77% in arms A and B, respectively (P = 0.084). The median number of aphereses needed to reach the yield of >= 3x10(6)/kg was lower in arm A than in arm B (1 vs 2, P = 0.035). Two patients needed plerixafor in arm A and five patients in arm B (P = 0.428). Although CY-based mobilization was more effective, G-CSF alone was successful in a great majority of patients to reach the defined collection target after three cycles of lenalidomide-based induction.Peer reviewe
Detection of circulating MUCIN 1 glycovariants from breast cancer patients using glycan-binding proteins coated on fluorescent nanoparticles
Anti-Tn antibody coated fluorescent nanoparticle-based immunoassay for the detection of mucin 1 in breast cancer patients
Potential role of glycovariants of urinary MUC1 and CEA in sensitive detection of urothelial bladder cancer
Protecting ITER walls: fast ion power loads in 3D magnetic field
The fusion alpha and beam ion with steady-state power loads in all four main operating scenarios of ITER have been evaluated by the ASCOT code. For this purpose, high-fidelity magnetic backgrounds were reconstructed, taking into account even the internal structure of the ferritic inserts and tritium breeding modules (TBM). The beam ions were found to be almost perfectly confined in all scenarios, and only the so-called hybrid scenario featured alpha loads reaching 0.5 MW due to its more triangular plasma. The TBMs were not found to jeopardize the alpha confinement, nor cause any hot spots. Including plasma response did not bring dramatic changes to the load. The ELM control coils (ECC) were simulated in the baseline scenario and found to seriously deteriorate even the beam confinement. However, the edge perturbation in this case is so large that the sources have to be re-evaluated with plasma profiles that take into account the ECC perturbation