Search results for "including"
showing 10 items of 642 documents
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…
Terrestrial Inputs Drive Seasonality in Organic Matter and Nutrient Biogeochemistry in a High Arctic Fjord System (Isfjorden, Svalbard)
2020
Climate-change driven increases in temperature and precipitation are leading to increased discharge of freshwater and terrestrial material to Arctic coastal ecosystems. These inputs bring sediments, nutrients and organic matter (OM) across the land-ocean interface with a range of implications for coastal ecosystems and biogeochemical cycling. To investigate responses to terrestrial inputs, physicochemical conditions were characterized in a river- and glacier-influenced Arctic fjord system (Isfjorden, Svalbard) from May to August in 2018 and 2019. Our observations revealed a pervasive freshwater footprint in the inner fjord arms, the geochemical properties of which varied spatially and seaso…
IGF2BP3 Associates with Proliferative Phenotype and Prognostic Features in B-Cell Acute Lymphoblastic Leukemia
2021
Simple Summary Although the prognosis of acute lymphoblastic leukemia (ALL) has improved significantly during the past decades, ALL remains a major cause of pediatric cancer mortality, and more accurate risk-stratification is required. We investigated IGF2BP3, which has previously been associated with aggressive cancers, and found high and subtype-specific expression of IGF2BP3 in B-cell ALL, that was associated with good outcome in high-risk patients. Results suggest that IGF2BP3 could be useful to improve stratification and prognosis of B-ALL. Abstract The oncofetal protein insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) belongs to a family of RNA-binding proteins involved i…
Macroalgal responses to ocean acidification depend on nutrient and light levels
2015
Ocean acidification may benefit algae that are able to capitalize on increased carbon availability for photosynthesis, but it is expected to have adverse effects on calcified algae through dissolution. Shifts in dominance between primary producers will have knock-on effects on marine ecosystems and will likely vary regionally, depending on factors such as irradiance (light vs. shade) and nutrient levels (oligotrophic vs. eutrophic). Thus experiments are needed to evaluate interactive effects of combined stressors in the field. In this study, we investigated the physiological responses of macroalgae near a CO2 seep in oligotrophic waters off Vulcano (Italy). The algae were incubated in situ …