RESUMO
Pancreatic and colorectal cancers are often KRAS mutated and are incurable when tumor DNA or protein persists or recurs after curative intent therapy. Cancer vaccine ELI-002 2P enhances lymph node delivery and immune response using amphiphile (Amph) modification of G12D and G12R mutant KRAS (mKRAS) peptides (Amph-Peptides-2P) together with CpG oligonucleotide adjuvant (Amph-CpG-7909). We treated 25 patients (20 pancreatic and five colorectal) who were positive for minimal residual mKRAS disease (ctDNA and/or serum tumor antigen) after locoregional treatment in a phase 1 study of fixed-dose Amph-Peptides-2P and ascending-dose Amph-CpG-7909; study enrollment is complete with patient follow-up ongoing. Primary endpoints included safety and recommended phase 2 dose (RP2D). The secondary endpoint was tumor biomarker response (longitudinal ctDNA or tumor antigen), with exploratory endpoints including immunogenicity and relapse-free survival (RFS). No dose-limiting toxicities were observed, and the RP2D was 10.0 mg of Amph-CpG-7909. Direct ex vivo mKRAS-specific T cell responses were observed in 21 of 25 patients (84%; 59% both CD4+ and CD8+); tumor biomarker responses were observed in 21 of 25 patients (84%); biomarker clearance was observed in six of 25 patients (24%; three pancreatic and three colorectal); and the median RFS was 16.33 months. Efficacy correlated with T cell responses above or below the median fold increase over baseline (12.75-fold): median tumor biomarker reduction was -76.0% versus -10.2% (P < 0.0014), and the median RFS was not reached versus 4.01 months (hazard ratio = 0.14; P = 0.0167). ELI-002 2P was safe and induced considerable T cell responses in patients with immunotherapy-recalcitrant KRAS-mutated tumors. ClinicalTrials.gov identifier: NCT04853017 .
Assuntos
Neoplasias Colorretais , Vacinas , Humanos , Proteínas Proto-Oncogênicas p21(ras)/genética , Recidiva Local de Neoplasia/patologia , Biomarcadores Tumorais/genética , Vacinas/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Peptídeos , Antígenos de Neoplasias/uso terapêuticoRESUMO
The current research aims to investigate whether perspective taking influences social tuning, or the alignment of one's self-views, explicit attitudes, and/or implicit attitudes with those of an interaction partner. In six different experiments, participants believed they would interact with a partner to complete a task. Prior to this ostensible interaction, participants were given a perspective taking mindset prime, or not, and information about their ostensible interaction partners views. Participants then completed attitude measures related to the partner's perceived views. Experiments 1a, 1b, and 2 examined whether perspective taking with an ostensible interaction partner who endorses gender traditional (or non-traditional) views align their self-views with this partner, including implicit self-views (Experiment 2). Experiments 3-5 investigated whether perspective taking leads to social tuning for egalitarian racial attitudes, including when the partner's expectations of how others will be and when the participant learns their ostensible IAT score at the beginning of the session. We predicted perspective takers would be more likely to social tune their explicit and implicit attitudes to the attitudes of their interaction partner than non-perspective takers. Across all experiments, perspective takers were more likely to social tune their self-views and explicit attitudes than non-perspective takers. However, social tuning never occurred for implicit attitudes. Thus, future research is needed to understand why perspective taking does not influence the tuning of implicit attitudes, but other motivations, like affiliative and epistemic, do.
RESUMO
BACKGROUND: Asthma is a common childhood illness with high morbidity and mortality among minority and socio-economically disadvantaged children. Disparities are not fully accounted for by differences in asthma prevalence, highlighting a need for interventions targeting factors associated with poorer asthma control. One such factor is psychological stress. OBJECTIVE: Here, we examine the feasibility and acceptability of "I Can Cope (ICC)," a school-based stress management and coping intervention for children with asthma. METHODS: A parallel randomized pilot trial was conducted. One hundred and four low-income children (mean age 10 years; 54% male; 70% African American) with persistent asthma were recruited from 12 urban schools and randomized to the following: (a) ICC or one of two control conditions: (b) "Open Airways for Schools (OAS)"-an asthma education intervention or (c) no treatment. RESULTS: Seventy one percentage of eligible children participated in the study, with a dropout rate of 12%. ICC was rated as highly acceptable by participating children and parents. Preliminary efficacy data suggest that when compared with no treatment, ICC resulted in decreased symptoms of depression, perceived stress and child-reported symptoms of asthma, and improvements in sleep quality and child-reported asthma control. There were no intervention-related changes in objective measures of asthma morbidity. The magnitude of intervention effects on psychological function did not differ between the ICC and OAS groups. CONCLUSIONS: Results support the feasibility and acceptability of utilizing school-based interventions to access hard to reach children with asthma. Preliminary findings offer support for future, large-scale efficacy studies of school-based interventions designed to target multiple factors that contribute to asthma disparities.
Assuntos
Adaptação Psicológica , Asma/epidemiologia , Educação de Pacientes como Assunto , Instituições Acadêmicas , Estudantes , Adolescente , Asma/etiologia , Asma/psicologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Serviços de Saúde Materno-Infantil , Projetos Piloto , Vigilância em Saúde Pública , Qualidade de Vida , Fatores Socioeconômicos , Estresse PsicológicoRESUMO
Parents of toddlers with an older sibling with autism spectrum disorder (ASD; high risk, HR) and parents of low risk (LR) toddlers with typically-developing older siblings read a wordless picture book to their child at 22 and 28 months. Parents' and toddlers' internal state language (ISL) was coded; parents reported on toddlers' use of ISL. Diagnostic assessments conducted at 36 months identified three groups: ASD, HR-noASD, LR. Parents did not differ in overall ISL, but parents of toddlers with later ASD attempted to elicit ISL from their children less than parents of LR toddlers. Toddlers increased their use of ISL with age, but those with ASD had lower scores and less age-related improvement than children in the other two groups.
Assuntos
Transtorno do Espectro Autista/terapia , Idioma , Pais , Adulto , Transtorno do Espectro Autista/genética , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Masculino , Psicoterapia/métodos , LeituraRESUMO
Children with autism spectrum disorder often demonstrate difficulties with self-regulation, although studies of this construct in young children with autism spectrum disorder are limited. In this study, developmental changes were examined using a measure of self-regulation appropriate for young children, resistance to temptation. At 22, 28, and 34 months, toddlers with an older sibling with autism spectrum disorder (high risk) and toddlers with typically developing older siblings (low risk) were presented with an appealing toy and instructed not to touch it. Observers coded whether or not children touched the toy and the strategies they used to resist touching it. At 36 months, children were assessed for autism spectrum disorder, yielding three groups: high risk children with autism spectrum disorder, high risk children without autism spectrum disorder, and low risk children. At 22 months, most children, regardless of group, touched the forbidden toy; at 28 and 34 months, many high risk children without autism spectrum disorder and low risk children resisted the temptation to touch the toy, whereas most of the children with autism spectrum disorder did not. Differences in delay strategies were also evident. Some, but not all group differences, were accounted for by differences in language ability. Results highlight one early index of impulse control that differentiates children with emerging autism spectrum disorder from age-mates prior to the third birthday.