Longitudinal clinico-genomic data generation, drugable target development and multi-sites validation for drug development enhancement
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE183984 | GEO | 2021/09/16
REPOSITORIES: GEO
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Project description:Longitudinal clinico-genomic data generation, drugable target development and multi-sites validation for drug development enhancement
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2007-09-12 | GSE8967 | GEO
Project description:3' RNA-seq of patient derived colon cancer xenograft models (N=10) showing initial disease control under cetuximab treatment were collected. All xenograft models were wildtype for KRAS, NRAS, BRAF and PIK3CA. All mice were treated with cetuximab (Merck Serono) by intra peritoneal (i.p.) injection twice per week and dosed at 25mg/kg to establish response characteristics. Tumors were chronically treated to establish cetuximab secondary resistant tumors .
2021-06-14 | GSE141861 | GEO
Project description:Global mRNA expression profiling of patient derived colon cancer xenograft models (N=10) showing disease control under cetuximab treatment were collected using Agilent human whole genome array (G4845A AMADID 026652, cRNA 4x44k V2) . All xenograft models were wildtype for KRAS, NRAS, BRAF and PIK3CA. All Mice were treated with cetuximab (Merck Serono) by intra peritoneal (i.p.) injection twice per week and dosed at 25mg/kg to establish response characteristics. Tumors were chronically treated to establish cetuximab secondary resistant tumors .
2021-05-21 | GSE140973 | GEO
Project description:Over recent years the role of biomarkers in anticancer drug development has expanded across a spectrum of applications ranging from research tool during early discovery to surrogate endpoint in the clinic. However, in Europe when biomarker measurements are performed on samples collected from subjects entered into clinical trials of new investigational agents, laboratories conducting these analyses become subject to the Clinical Trials Regulations. While these regulations are not specific in their requirements of research laboratories, quality assurance and in particular assay validation are essential. This review, therefore, focuses on a discussion of current thinking in biomarker assay validation. Five categories define the majority of biomarker assays from 'absolute quantitation' to 'categorical'. Validation must therefore take account of both the position of the biomarker in the spectrum towards clinical end point and the level of quantitation inherent in the methodology. Biomarker assay validation should be performed ideally in stages on 'a fit for purpose' basis avoiding unnecessarily dogmatic adherence to rigid guidelines but with careful monitoring of progress at the end of each stage. These principles are illustrated with two specific examples: (a) absolute quantitation of protein biomarkers by mass spectrometry and (b) the M30 and M65 ELISA assays as surrogate end points of cell death.
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Project description:Starting from childhood, the human brain restructures and rewires throughout life. Characterizing such complex brain development requires effective analysis of longitudinal and multi-modal neuroimaging data. Here, we propose such an analysis approach named Longitudinal Correlation Analysis (LCA). LCA couples the data of two modalities by first reducing the input from each modality to a latent representation based on autoencoders. A self-supervised strategy then relates the two latent spaces by jointly disentangling two directions, one in each space, such that the longitudinal changes in latent representations along those directions are maximally correlated between modalities. We applied LCA to analyze the longitudinal T1-weighted and diffusion-weighted MRIs of 679 youths from the National Consortium on Alcohol and Neurodevelopment in Adolescence. Unlike existing approaches that focus on either cross-sectional or single-modal modeling, LCA successfully unraveled coupled macrostructural and microstructural brain development from morphological and diffusivity features extracted from the data. A retesting of LCA on raw 3D image volumes of those subjects successfully replicated the findings from the feature-based analysis. Lastly, the developmental effects revealed by LCA were inline with the current understanding of maturational patterns of the adolescent brain.
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Project description:Empathy involves feeling compassion for others and imagining how they feel. In this article, we develop and validate the Single Item Trait Empathy Scale (SITES), which contains only one item that takes seconds to complete. In seven studies (N=5,724), the SITES was found to be both reliable and valid. It correlated in expected ways with a wide variety of intrapersonal outcomes. For example, it is negatively correlated with narcissism, depression, anxiety, and alexithymia. In contrast, it is positively correlated with other measures of empathy, self-esteem, subjective well-being, and agreeableness. The SITES also correlates with a wide variety of interpersonal outcomes, especially compassion for others and helping others. The SITES is recommended in situations when time or question quantity is constrained.
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Project description:First line chemotherapy with platinum and cetuximab is usually offered to RM-HNSCC pts. In the Extreme trial a median progression free survival (PFS) time of 5.6 months was reported. However, a small fraction of pts achieves a prolonged PFS (> than 12 months). Till now, no recognized predictive biological factor has been identified.
2016-08-01 | GSE65021 | GEO
Project description:Platinum-based chemotherapy plus cetuximab, an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody (Mab), is usually offered to recurrent/metastatic (R/M) head-neck squamous cell carcinoma (HNSCC) patients, with only a small portion experiencing durable responses. The anti-EGFR-Mab panitumumab, was used as single agent in platinum pre-treated R/M-HNSCC patients in a phase II trial (PANI01). By analyzing gene expression profiles of a selected retrospective series of HNSCC patients treated with cetuximab, an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody (MAb), associated to chemotherapy, we were able to propose that long progression-free survival (PFS) cases consistently belong to defined molecular subtypes, such as Cluster3-hypoxia and Basal subtypes, respectively defined by De Cecco et al [DeCecco; Oncotarget, 2015] and Keck et al [Keck; CCR,2015], while short-PFS cases are characterized by an over-activation of RAS signaling
2019-01-23 | GSE102995 | GEO
Project description:BackgroundMultimorbidity is recognized as a major public health issue that increases with age and affects approximately two-thirds of older people in Canada, the US, Australia and many European countries. This study develops and tests a three domain (functional, social and psychological) multimorbidity resilience composite index based on a previously developed lifecourse model of multimorbidity resilience, incorporating measures of adversity and positive adaptation. The criterion validity of the measure is demonstrated by means of an analysis of key outcome variables drawn from the literature.MethodsWe used the baseline data from the Comprehensive Cohort of the Canadian Longitudinal Study on Aging. Associations of functional, social, psychological as well as total resilience with two health utilization and three illness context outcome variables were examined using logistic regression analyses, adjusted for age, gender, marital status, income, education, region, and number of chronic conditions.ResultsThe sample included all 6771 Canadian adults aged 65 or older (mean age 73.0, 57% women) who reported two or more of 27 possible chronic conditions. Total resilience was associated with: perceived health (OR = 1.68, CI 1.59-1.77); sleep quality (OR = 1.34, CI 1.30-1.38); perceived pain (OR = 0.80, CI 0.77-0.83); hospital overnight stays (OR = 0.87, CI 0.83-0.91); and emergency department visits (OR = 0.90, CI 0.87-0.94)., after adjusting for socio-demographic factors, and number of chronic conditions. These associations were similar for the unadjusted models, as well as for the functional, social and psychological resilience sub-indices.ConclusionsCombining components of adversity and positive adaptation within functional, social and psychological domains produces a measure of multimorbidity resilience that is associated with more positive health outcomes. Several implications of a composite multimorbidity resilience measure for clinical practice are identified. This measure can be replicated using measures found in other secondary health data sets. Future validation using longitudinal data is warranted.
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