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PubMed Journals Articles About "Genocea Preclinical Data SITC Demonstrate That Inhibitory Neoantigens" RSS

03:55 EST 11th December 2019 | BioPortfolio

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Showing "Genocea Preclinical Data SITC Demonstrate that Inhibitory Neoantigens" PubMed Articles 1–25 of 33,000+

NeoFuse: predicting fusion neoantigens from RNA sequencing data.

Gene fusions can generate immunogenic neoantigens that mediate anticancer immune responses. However, their computational prediction from RNA sequencing (RNA-seq) data requires deep bioinformatics expertise to assembly a computational workflow covering the prediction of: fusion transcripts, their translated proteins and peptides, Human Leukocyte Antigen (HLA) types, and peptide-HLA binding affinity. Here, we present NeoFuse, a computational pipeline for the prediction of fusion neoantigens from tumor RNA-seq...


Identification of neoantigens derived from alternative splicing and RNA modification.

The acquisition of somatic mutations is the most common event in cancer. Neoantigens expressed from genes with mutations acquired during carcinogenesis can be tumor-specific. Since the immune system recognizes tumor-specific peptides, they are potential targets for personalized neoantigen-based immunotherapy. However, the discovery of druggable neoantigens remains challenging, suggesting that a deeper understanding of the mechanism of neoantigen generation and better strategies to identify them will be requ...

Tumor antigenS heterogeneity and immune response-targeting neoantigens in breast cancer.

Breast cancer is both the most common type of cancer and the most frequent cause of cancer mortality in women, mainly because of its heterogeneity and limited immunogenicity. The aim of specific active cancer immunotherapy is to stimulate the host's immune response against cancer cells directly using a vaccine platform carrying one or more tumor antigens. In particular, the ideal tumor antigen should be able to elicit T cell and B cell responses, be specific for the tumor and be expressed at high levels on ...


Neoantigen Dissimilarity to the Self-Proteome Predicts Immunogenicity and Response to Immune Checkpoint Blockade.

Despite improved methods for MHC affinity prediction, the vast majority of computationally predicted tumor neoantigens are not immunogenic experimentally, indicating that high-quality neoantigens are beyond current algorithms to discern. To enrich for neoantigens with the greatest likelihood of immunogenicity, we developed an analytic method to parse neoantigen quality through rational biological criteria across five clinical datasets for 318 cancer patients. We explored four quality metrics, including anal...

Tumor Neoantigens: When Too Much of a Good Thing Is Bad.

Immunotherapy has been the most effective in tumors with high mutational burden. However, a recent study in Cell by Wolf et al. demonstrates that high intratumor heterogeneity (ITH) for cancer neoantigens paradoxically attenuates anti-tumor immune responses, suggesting a need to quantify ITH to improve patient selection for checkpoint blockade therapy.

Alternative tumour-specific antigens.

The study of tumour-specific antigens (TSAs) as targets for antitumour therapies has accelerated within the past decade. The most commonly studied class of TSAs are those derived from non-synonymous single-nucleotide variants (SNVs), or SNV neoantigens. However, to increase the repertoire of available therapeutic TSA targets, 'alternative TSAs', defined here as high-specificity tumour antigens arising from non-SNV genomic sources, have recently been evaluated. Among these alternative TSAs are antigens deriv...

Navigation-guided osteotomies improve margin delineation in tumors involving the sinonasal area: A preclinical study.

To demonstrate and quantify, in a preclinical setting, the benefit of three-dimensional (3D) navigation guidance for margin delineation during ablative open surgery for advanced sinonasal cancer.

Identification of a Core Amino Acid Motif within the α Subunit of GABARs that Promotes Inhibitory Synaptogenesis and Resilience to Seizures.

The fidelity of inhibitory neurotransmission is dependent on the accumulation of γ-aminobutyric acid type A receptors (GABARs) at the appropriate synaptic sites. Synaptic GABARs are constructed from α(1-3), β(1-3), and γ2 subunits, and neurons can target these subtypes to specific synapses. Here, we identify a 15-amino acid inhibitory synapse targeting motif (ISTM) within the α2 subunit that promotes the association between GABARs and the inhibitory scaffold proteins collybistin and gephyrin. Using mic...

Sesquiterpenoids from and their NO production inhibitory activity in RAW264.7 cells.

Investigation into the chemical diversity of led to the discovery of two new (, ) and four known (, -) sesquiterpenoids. The new structures were determined extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC values rang...

Polyoxometalates: Study of inhibitory kinetics and mechanism against α-glucosidase.

Alpha-glucosidase is considered to be an important target for the treatment of noninsulin-dependent diabetes. In this work, the inhibitory effects of polyoxometalates (POMs) affected by three different factors (heteroatom, transition metal substitution element and vanadium substitution number) on α-glucosidase were studied. We found that POMs with Keggin-type and vanadium-substituted Dawson-type structures act as effective and mostly competitive inhibitors for α-glucosidase (IC values around 40-160 μM)...

Cardiovascular risk of electronic cigarettes: a review of preclinical and clinical studies.

Cigarette smoking is the most preventable risk factor related to cardiovascular morbidity and mortality. Tobacco usage has declined in recent years; however, the use of alternative nicotine delivery methods, particularly e-cigarettes, has increased exponentially despite limited data on their short- and long-term safety and efficacy. Due to their unique properties, the impact of e-cigarettes on cardiovascular physiology is not fully known. Here, we summarize both preclinical and clinical data extracted from ...

Patterns of immune-cell infiltration in murine models of melanoma: roles of antigen and tissue site in creating inflamed tumors.

Immune-cell infiltration is associated with improved survival in melanoma. Human melanoma metastases may be grouped into immunotypes representing patterns of immune-cell infiltration: A (sparse), B (perivascular cuffing), and C (diffuse). Immunotypes have not been defined for murine melanomas, but may provide opportunities to understand mechanism-driving immunotype differences. We performed immunohistochemistry with immune-cell enumeration, immunotyping, and vascular density scoring in genetically engineere...

Mutual Inhibition with Few Inhibitory Cells via Nonlinear Inhibitory Synaptic Interaction.

In computational neural network models, neurons are usually allowed to excite some and inhibit other neurons, depending on the weight of their synaptic connections. The traditional way to transform such networks into networks that obey Daleâs law (i.e., a neuron can either excite or inhibit) is to accompany each excitatory neuron with an inhibitory one through which inhibitory signals are mediated. However, this requires an equal number of excitatory and inhibitory neurons, whereas a realistic number of in...

Triterpenoids from Ainsliaea latifolia and Their Cyclooxyenase-2 (COX-2) Inhibitory Activities.

Eight new triterpenoids were isolated from Ainsliaea latifolia. The structures of these compounds were elucidated by interpretation of spectroscopic data, including HRESIMS and NMR data. Compounds 4-6 are identified as rare trinorcucurbitane or tetranorcucurbitane triterpenoids. The absolute configurations of compounds 1 and 2 were confirmed by Snatzke's method. All compounds were evaluated for their inhibition against cyclooxyenase-2 (COX-2), in which compound 4 showed significant inhibitory effect against...

Capillary rarefaction is more closely associated with CKD progression after cisplatin, rhabdomyolysis, and ischemia reperfusion-induced AKI than renal fibrosis.

Acute kidney injury (AKI) is a strong independent predictor of mortality, and often results in incomplete recovery of renal function, leading to progressive chronic kidney disease (CKD). Many clinical trials have been conducted based on promising preclinical data, but no therapeutic interventions have been shown to improve long-term outcomes after AKI. This is partly due to the failure of preclinical studies to accurately model clinically relevant injury and long-term outcomes on CKD progression. Here, we e...

Sexual dimorphism of Inhibitory Synaptic Transmission in RA Projection Neurons of Songbirds.

The song control system in the brain of songbirds is important for the production and acquisition of song and exhibits some of the largest neural sex differences observed in vertebrates. The robust nucleus of the arcopallium (RA) is a premotor nucleus, playing a key role in controlling singing. RA projection neurons (PNs) receives denser synapse inputs including excitatory in males than in females. However, the inhibitory synaptic transmission in the RA has not been reported. In the present study, using who...

Interaction mechanism between α-glucosidase and A-type trimer procyanidin revealed by integrated spectroscopic analysis techniques.

α-Glucosidase is an important enzyme in human intestine, and inhibition of its activity can lower blood sugar levels to effectively prevent hyperglycaemia induced tissue damage. Here, we investigated the inhibitory activities of procyanidins with different structures on α-glucosidase and the underlying mechanism. The results showed that the IC of catechin and compounds 2-7 on α-glucosidase was lower than that of acarbose. A-type procyanidins might have better inhibitory activity than B-type procyanidins....

Human neutrophil elastase (HNE) inhibitory polyprenylated acylphloroglucinols from the flowers of Hypericum ascyron.

In the course of an investigation of human neutrophil elastase (HNE) associated with inflammation, the extract of the flower parts of Hypericum ascyron showed a significant influence to HNE. The responsible metabolites to HNE inhibition were found to be eight polyprenylated acylphloroglucinols, PPAPs (1-8) which showed IC ranges between 2.4 and 19.9 μM. This is the first report to demonstrate that PPAP skeleton exhibits potent HNE inhibition. The compounds 1-3 were characterized and newly named as ascyro...

Secondary Metabolites and PI3K Inhibitory Activity of Colletotrichum gloeosporioides, a Fungal Endophyte of Uncaria rhynchophylla.

In the present study, nine compounds (1-9) were isolated from Colletotrichum gloeosporioides (an endophytic fungus from Uncaria rhynchophylla) which was cultured in wheat bran medium. Their structures were elucidated as 4-Epi-14-hydroxy-10, 23-dihydro-24, 25-dehydroaflavinine (1), 10, 23-Dihydro-24,25 -dehydro-21-oxoaflavinine (2), Ergosterol (3), Ergosterol peroxide (4), Mellein (5), 4, 5-dihydroblumenol A (6), Colletotrichine A (7), Cyclo(L-leucyl-L-leucyl) (8), and Brevianamide F (9) based on NMR spectra...

The development of inhibitory control in adolescence and prospective relations with delinquency.

Despite the central role of inhibitory control in models of adolescent development, few studies have examined the longitudinal development of inhibitory control within adolescence and its prospective association with maladaptive outcomes. The current study evaluated: 1) growth in inhibitory control from early- to middle-adolescence, and 2) the relation between inhibitory control and later delinquency.

Assessment of Striatal Dopamine Transporter Binding in Individuals With Major Depressive Disorder: In Vivo Positron Emission Tomography and Postmortem Evidence.

Major depressive disorder (MDD) might involve dopamine (DA) reductions. The DA transporter (DAT) regulates DA clearance and neurotransmission and is sensitive to DA levels, with preclinical studies (including those involving inescapable stressors) showing that DAT density decreases when DA signaling is reduced. Despite preclinical data, evidence of reduced DAT in MDD is inconclusive.

Reporting preclinical anesthesia study (REPEAT): Evaluating the quality of reporting in the preclinical anesthesiology literature.

Poor reporting quality may contribute to irreproducibility of results and failed 'bench-to-bedside' translation. Consequently, guidelines have been developed to improve the complete and transparent reporting of in vivo preclinical studies. To examine the impact of such guidelines on core methodological and analytical reporting items in the preclinical anesthesiology literature, we sampled a cohort of studies. Preclinical in vivo studies published in Anesthesiology, Anesthesia & Analgesia, Anaesthesia, and t...

Assessing and Raising Concerns About Duplicate Publication, Authorship Transgressions and Data Errors in a Body of Preclinical Research.

Authorship transgressions, duplicate data reporting and reporting/data errors compromise the integrity of biomedical publications. Using a standardized template, we raised concerns with journals about each of these characteristics in 33 pairs of publications originating from 15 preclinical (animal) trials reported by a group of researchers. The outcomes of interest were journal responses, including time to acknowledgement of concerns, time to decision, content of decision letter, and disposition of publicat...

Exposure-response analysis of drug-induced QT interval prolongation in telemetered monkeys for translational prediction to human.

The preclinical in vivo assay for QT prolongation is critical for predicting torsadogenic risk, but still difficult to extrapolate to humans. This study ran preclinical tests in cynomolgus monkeys on seven QT reference drugs containing the drugs used in the IQ-CSRC clinical trial and applied exposure-response (ER) analysis to the data to investigate the potential for translational information on the QT effect.

Neurofilament light chain plasma concentration predicts neurodegeneration and clinical progression in nondemented elderly adults.

Previous studies demonstrated that plasma neurofilament light chain (NFL) played important predictive roles in disease progression and neurodegeneration in the preclinical phase of familial Alzheimer's disease (AD). However, whether plasma NFL has the same predictive roles in sporadic AD is still unclear. In this study, 243 cognitively normal (CN) participants from the ADNI database were divided into two subgroups (CN- and CN+) according to CSF Aβ or AV45-PET. Associations of baseline plasma NFL concentrat...


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