Immune checkpoint inhibitors in pmmr metastatic colorectal cancer: A tough challenge

The introduction of checkpoint inhibitors provided remarkable achievements in several solid tumors but only 5% of metastatic colorectal cancer (mCRC) patients, i.e., those with bearing microsatellite instable (MSI-high)/deficient DNA mismatch repair (dMMR) tumors, benefit from this approach. The favorable effect of immunotherapy in these patients has been postulated to be due to an increase in neoantigens due to their higher somatic mutational load, also associated with an abundant infiltration of immune cells in tumor microenvironment (TME). While in patients with dMMR tumors checkpoint inhibitors allow achieving durable response with dramatic survival improvement, current results in patients with microsatellite stable (MSS or MSI-low)/proficient DNA mismatch repair (pMMR) tumors are disappointing. These tumors show low mutational load and absence of “immune-competent” TME, and are intrinsically resistant to immune checkpoint inhibitors. Modifying the interplay among cancer cells, TME and host immune system is the aim of multiple lines of research in order to enhance the immunogenicity of pMMR mCRC, and exploit immunotherapy also in this field. Here, we focus on the rationale behind ongoing clinical trials aiming at extending the efficacy of immunotherapy beyond the MSI-high/dMMR subgroup with particular regard to academic no-profit studies

Primary tumor sidedness and benefit from FOLFOXIRI plus bevacizumab as initial therapy for metastatic colorectal cancer. Retrospective analysis of the TRIBE trial by GONO

Right-sided metastatic colorectal cancer (mCRC) patients have poor prognosis and achieve limited benefit from first-line doublets plus a targeted agent. In this unplanned analysis of the TRIBE study, we investigated the prognostic and predictive impact of primary tumor sidedness in mCRC patients and the differential impact of the intensification of the chemotherapy in subgroups defined according to both primary tumor sidedness and RAS and BRAF mutational status

High--order connected moments expansion for the Rabi Hamiltonian

We analyze the convergence properties of the connected moments expansion (CMX) for the Rabi Hamiltonian. To this end we calculate the moments and connected moments of the Hamiltonian operator to a sufficiently large order. Our large--order results suggest that the CMX is not reliable for most practical purposes because the expansion exhibits considerable oscillations.Comment: 12 pages, 5 figures, 1 tabl

3D acoustic propagation through an estuarine salt wedge at low-to-mid-frequencies: Modeling and measurement

Author Posting. © Acoustical Society of America, 2019. This article is posted here by permission of Acoustical Society of America for personal use, not for redistribution. The definitive version was published in Journal of the Acoustical Society of America 146(3),(2019): 1888-1902, doi:10.1121/1.5125258.The estuarine salt wedge presents a dynamic and highly refractive waveguide, the acoustic propagation characteristics of which are controlled by the water column sound speed gradient and boundary interactions. Acoustically, the salt wedge consists of two isospeed layers separated by a thin, three-dimensional (3D), high-gradient layer. The behavior of a broadband (500–2000 Hz) acoustic field under the influence of an estuarine salt wedge in the Columbia River estuary is explored using two 3D acoustic propagation models: 3D rays and 3D parabolic equation. These model results are compared to data collected during the field experiment. Results demonstrate that the dominant physical mechanism controlling acoustic propagation in this waveguide shifts from 3D bottom scatter in a non-refractive waveguide (before the entrance of the salt wedge) to 3D acoustic refraction with minimal bottom interaction in a refractive waveguide (when the salt wedge occupies the acoustic transect). Vertical and horizontal refraction in the water column and out-of-plane scattering by the bottom are clearly evident at specific narrowband frequencies; however, these mechanisms contribute to, but do not account for, the total observed broadband transmission loss.Environmental input to the acoustic models included high resolution bathymetric survey data provided by Guy Gelfenbaum (USGS), and modeled temperature and salinity profiles of the water column provided by Antonio Baptista, Charles Seaton, and Paul Turner at CMOP. The authors thank Derek Olson (NPS) for invaluable assistance with running the 3DPE model on NPS HPC resources. This work was supported by the Office of Naval Research.2020-03-3

Investigation of AIRSAR signatures of the Gulf Stream

Extensive Airborne Synthetic Aperture Radar (AIRSAR) measurements were made on 20 July 1990 during the NRL Gulf Stream (GS) experiment which addressed a number of scientific questions relating to SAR imaging of the ocean surface in the presence of variable currents and the background thermohaline circulation. The nature of the electromagnetic (e.m.) backscatter from the North edge of the GS using polarimetric signatures and amplitude imagery from the AIRSAR data is addressed

Clinical and molecular determinants of extrahepatic disease progression (ePD) in initially unresectable, liver-limited metastatic colorectal cancer (mCRC)

e15511Background: In the last years, availability of active upfront systemic regimens, development of surgical techniques and diffusion of locoregional treatments (LrTx) increased the therapeutic o..

lba20tribe2 a phase iii randomized strategy study by gono in the 1st and 2nd line treatment of unresectable metastatic colorectal cancer mcrc patients pts

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molecular characterization of immune microenvironment in colorectal cancers with microsatellite instability by digital rna counting

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development of a new clinical nomogram including velocity rate of disease progression to predict outcome in metastatic colorectal cancer patients treated with bevacizumab beyond progression a subanalysis from tribe trial

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folfoxiri plus bevacizumab bev followed by maintenance with bev alone or bev plus metronomic chemotherapy metroct in mcrc final results of the phase ii randomized moma trial by gono

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