21 research outputs found
Comprehensive Genomic Profiling in Routine Clinical Practice Leads to a Low Rate of Benefit from Genotype-Directed Therapy
Background: Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options.
Methods: Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT.
Results: A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease.
Conclusions: CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT
Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy
Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT®), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel
Reflexion and reflection: A social cognitive neuroscience approach to attributional inference
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Comprehensive genomic profiling in routine clinical practice leads to a low rate of benefit from genotype-directed therapy
Abstract Background Describe a single-center real-world experience with comprehensive genomic profiling (CGP) to identify genotype directed therapy (GDT) options for patients with malignancies refractory to standard treatment options. Methods Patients who had CGP by a CLIA-certified laboratory between November 2012 and December 2015 were included. The medical records were analyzed retrospectively after Institutional Review Board (IRB) approval. The treating oncologist made the decision to obtain the assay to provide potential therapeutic options. The objectives of this study were to determine the proportion of patients who benefited from GDT, and to identify barriers to receiving GDT. Results A total of 125 pediatric and adult patients with a histologically confirmed diagnosis of malignancy were included. Among these, 106 samples were from adult patients, and 19 samples were from pediatric patients. The median age was 54 years for adults. The majority had stage IV malignancy (53%) and were pretreated with 2–3 lines of therapy (45%). The median age was 8 years for pediatric patients. The majority had brain tumors (47%) and had received none or 1 line of therapy (58%) when the profiling was requested. A total of 111 (92%) patients had genomic alterations and were candidates for GDT either via on/off-label use or a clinical trial (phase 1 through 3). Fifteen patients (12%) received GDT based on these results including two patients who were referred for genomically matched phase 1 clinical trials. Three patients (2%) derived benefit from their GDT that ranged from 2 to 6 months of stable disease. Conclusions CGP revealed potential treatment options in the majority of patients profiled. However, multiple barriers to therapy were identified, and only a small minority of the patients derived benefit from GDT
Caffeine attenuates practice effects in word stem completion as measured by fMRI BOLD signal
Incorporation and Controlled Release of Silyl Ether Prodrugs from PRINT Nanoparticles
Asymmetric bifunctional silyl ether (ABS) prodrugs of
chemotherapeutics
were synthesized and incorporated within 200 nm Ă— 200 nm particles.
ABS prodrugs of gemcitabine were selected as model compounds because
of the difficulty to encapsulate a water-soluble drug within a hydrogel.
The resulting drug delivery systems were degraded under acidic conditions
and were found to release only the parent or active drug. Furthermore,
changing the steric bulk of the alkyl substituents on the silicon
atom could regulate the rate of drug release and, therefore, the intracellular
toxicity of the gemcitabine-loaded particles. This yielded a family
of novel nanoparticles that could be tuned to release drug over the
course of hours, days, or months
The impact of learner characteristics on training transfer expectation: a survey of Thai teachers’ perception of cloud computing tools
Particle Replication in Nonwetting Templates Nanoparticles with Tumor Selective Alkyl Silyl Ether Docetaxel Prodrug Reduces Toxicity
Delivery systems designed to have
triggered release after passively
targeting the tumor may improve small molecule chemotherapeutic delivery.
Particle replication in nonwetting templates was used to prepare nanoparticles
to passively target solid tumors in an A549 subcutaneous xenograft
model. An acid labile prodrug was delivered to minimize systemic free
docetaxel concentrations and improve tolerability without compromising
efficacy
Nanoparticle drug loading as a design parameter to improve docetaxel pharmacokinetics and efficacy
Nanoparticle (NP) drug loading is one of the key defining characteristics of a NP formulation. However, the effect of NP drug loading on therapeutic efficacy and pharmacokinetics has not been thoroughly evaluated. Herein, we characterized the efficacy, toxicity and pharmacokinetic properties of NP docetaxel formulations that have differential drug loading but are otherwise identical. Particle Replication in Non-wetting Templates (PRINT(®)), a soft-lithography fabrication technique, was used to formulate NPs with identical size, shape and surface chemistry, but with variable docetaxel loading. The lower weight loading (9%-NP) of docetaxel was found to have a superior pharmacokinetic profile and enhanced efficacy in a murine cancer model when compared to that of a higher docetaxel loading (20%-NP). The 9%-NP docetaxel increased plasma and tumor docetaxel exposure and reduced liver, spleen and lung exposure when compared to that of 20%-NP docetaxel