Search results for "LUDI"

A point mutation in the Ncr1 signal peptide impairs the development of innate lymphoid cell subsets.

2018

International audience; NKp46 (CD335) is a surface receptor shared by both human and mouse natural killer (NK) cells and innate lymphoid cells (ILCs) that transduces activating signals necessary to eliminate virus-infected cells and tumors. Here, we describe a spontaneous point mutation of cysteine to arginine (C14R) in the signal peptide of the NKp46 protein in congenic Ly5.1 mice and the newly generated NCR(B6C14R) strain. Ly5.1(C14R) NK cells expressed similar levels of Ncr1 mRNA as C57BL/6, but showed impaired surface NKp46 and reduced ability to control melanoma tumors in vivo. Expression of the mutant NKp46(C14R) in 293T cells showed that NKp46 protein trafficking to the cell surface …

Bovine herpesvirus 4-based vector delivering the full length xCT DNA efficiently protects mice from mammary cancer metastases by targeting cancer ste…

2018

Despite marked advancements in its treatment, breast cancer is still the second leading cause of cancer death in women, due to relapses and distal metastases. Breast cancer stem cells (CSCs), are a cellular reservoir for recurrence, metastatic evolution and disease progression, making the development of novel therapeutics that target CSCs, and thereby inhibit metastases, an urgent need. We have previously demonstrated that the cystine-glutamate antiporter xCT (SLC7A11), a protein that was shown to be overexpressed in mammary CSCs and that plays a key role in the maintenance of their redox balance, self-renewal and resistance to chemotherapy, is a potential target for mammary cancer immunoth…

Evolution of melanoma cross-resistance to CD8⁺ T cells and MAPK inhibition in the course of BRAFi treatment

2018

The profound but frequently transient clinical responses to BRAFV600 inhibitor (BRAFi) treatment in melanoma emphasize the need for combinatorial therapies. Multiple clinical trials combining BRAFi and immunotherapy are under way to further enhance therapeutic responses. However, to which extent BRAFV600 inhibition may affect melanoma immunogenicity over time remains largely unknown. To support the development of an optimal treatment protocol, we studied the impact of prolonged BRAFi exposure on the recognition of melanoma cells by T cells in different patient models. We demonstrate that autologous CD8+ tumor-infiltrating lymphocytes (TILs) efficiently recognized short-term (3, 7 days) BRAF…

A multicenter phase 1 study of solitomab (MT110, AMG 110), a bispecific EpCAM/CD3 T-cell engager (BiTE®) antibody construct, in patients with refract…

2018

ABSTRACT We assessed the tolerability and antitumor activity of solitomab, a bispecific T-cell engager (BiTE®) antibody construct targeting epithelial cell adhesion molecule (EpCAM). Patients with relapsed/refractory solid tumors not amenable to standard therapy received solitomab as continuous IV infusion in a phase 1 dose-escalation study with six different dosing schedules. The primary endpoint was frequency and severity of adverse events (AEs). Secondary endpoints included pharmacokinetics, pharmacodynamics, immunogenicity, and antitumor activity. Sixty-five patients received solitomab at doses between 1 and 96 µg/day for ≥28 days. Fifteen patients had dose-limiting toxicities (DLTs): e…

Responsiveness to anti-PD-1 and anti-CTLA-4 immune checkpoint blockade in SB28 and GL261 mouse glioma models.

2018

Immune checkpoint blockade (ICB) is currently evaluated in patients with glioblastoma (GBM), based on encouraging clinical data in other cancers, and results from studies with the methylcholanthrene-induced GL261 mouse glioma. In this paper, we describe a novel model faithfully recapitulating some key human GBM characteristics, including low mutational load, a factor reported as a prognostic indicator of ICB response. Consistent with this observation, SB28 is completely resistant to ICB, contrasting with treatment sensitivity of the more highly mutated GL261. Moreover, SB28 shows features of a poorly immunogenic tumor, with low MHC-I expression and modest CD8(+) T-cell infiltration, suggest…

Toma de decisiones en el paciente diagnosticado de tumor cerebral. A propósito de un caso clínico

2007

Pilar.Barreto@uv.es Justificación: La decisión sobre la alternativa terapéutica más conveniente, que corresponde al paciente asesorado por el equipo sanitario, se hace especialmente difícil en casos del mal pronóstico. Pacientes: Paciente joven con tumor cerebral, reintervenido en diversas ocasiones, al que se detecta una recidiva. Resultados: En contra de la opinión del equipo multidisciplinar, el paciente decide someterse a una reintervención, falleciendo a los cuatro meses presentando una calidad de vida aceptable. Conclusiones: Se plantea la necesidad, a través de un counselling adecuado, de permitir que el paciente escoja el resultado clínico preferido tras la transmisión clara de las …

Method for Reproducible Shipboard Segmented Flow Analysis Ammonium Measurement Using an In-House Reference Material for Quality Control

2021

Ammonium is a fundamental nutrient for phytoplankton growth in seawater and is a key component of the microbial loop. Ammonium measured in parallel with other nutrients is crucial in understanding the small temporal scale changes in oceanographic ecology. Despite the importance of measuring ammonium at sea, owing to its lability, there is no consensus on the best method. The lack of availability of certified reference materials for ammonium in seawater also makes it difficult to assess the accuracy and reproducibility of ammonium measurements. In this study we present a modified segmented flow analysis method using ortho-phthaldialdehyde (OPA) with fluorescence detection to measure ammonium…

Retention forestry and biodiversity conservation: a parallel with agroforestry

2013

In forested landscapes two general management systems – retention forestry and agroforestry – have been proposed as potentially efficient components of landscape approaches to ease the conflict between biodiversity objectives and human needs. In two recent reviews, Gustafsson et al. (2012) and Lindenmayer et al. (2012) provide a global overview of current knowledge about the practice and ecological roles of retention forestry. A few years ago, Bhagwat et al. (2008) produced a similar review addressing the role of agroforestry in biodiversity conservation. Here we draw a parallel between research on the ecological effects of retention forestry and agroforestry. We argue that conservation sci…

Kaanonien kaatama? : Johann Gottfried Waltherin elämä

2006

Tiešsaistes sludinājumu platformu lietojamība

2021

Latvijā ir radītas neskaitāmas tiešsaistes sludinājumu platformas, bet tikai retā ir spējīga veidot vērā ņemamu lietotāju pulku. Digitālajā vidē dizainam ir liela nozīme pastāvīgu lietotāju piesaistei. Dizains atbild par to, kā digitālais produkts izskatīsies un cik ērti lietojams tas būs. Starp aktuālākajām sludinājumu platformām Latvijā ir redzami dažādas stilistikas dizaini, bet visi kā viens ir ērti lietojami. Šajā darbā tiek apskatīti, pēc autora domām, digitālajā vidē būtiski dizaina un lietojamības principi, tad tiek analizētas dažādas sludinājumu platformas, ņemot vērā izpētītos lietojamības un dizaina principus. Balstoties uz iegūto informāciju tiek izstrādāts tiešsaistes suldināju…