848 research outputs found
sj-docx-3-tam-10.1177_17588359221081075 – Supplemental material for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment
No full textSupplemental material, sj-docx-3-tam-10.1177_17588359221081075 for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment by Stefan A. J. Buck, C. Louwrens Braal, Maaike M. Hofman, Esther Oomen-de Hoop, Peter de Bruijn, Inge M. Ghobadi Moghaddam-Helmantel, Koen G. A. M. Hussaarts, Mijntje B. Vastbinder, Quirine C. van Rossum-Schornagel, Ron H. N. van Schaik, Agnes Jager, Stijn L. W. Koolen and Ron H. J. Mathijssen in Therapeutic Advances in Medical Oncology</p
sj-docx-1-tam-10.1177_17588359221081075 – Supplemental material for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment
No full textSupplemental material, sj-docx-1-tam-10.1177_17588359221081075 for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment by Stefan A. J. Buck, C. Louwrens Braal, Maaike M. Hofman, Esther Oomen-de Hoop, Peter de Bruijn, Inge M. Ghobadi Moghaddam-Helmantel, Koen G. A. M. Hussaarts, Mijntje B. Vastbinder, Quirine C. van Rossum-Schornagel, Ron H. N. van Schaik, Agnes Jager, Stijn L. W. Koolen and Ron H. J. Mathijssen in Therapeutic Advances in Medical Oncology</p
sj-docx-2-tam-10.1177_17588359221081075 – Supplemental material for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment
No full textSupplemental material, sj-docx-2-tam-10.1177_17588359221081075 for Influence of probenecid on endoxifen systemic exposure in breast cancer patients on adjuvant tamoxifen treatment by Stefan A. J. Buck, C. Louwrens Braal, Maaike M. Hofman, Esther Oomen-de Hoop, Peter de Bruijn, Inge M. Ghobadi Moghaddam-Helmantel, Koen G. A. M. Hussaarts, Mijntje B. Vastbinder, Quirine C. van Rossum-Schornagel, Ron H. N. van Schaik, Agnes Jager, Stijn L. W. Koolen and Ron H. J. Mathijssen in Therapeutic Advances in Medical Oncology</p
Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy
Get PDFTamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate
sj-docx-1-tam-10.1177_17588359221103212 – Supplemental material for Improving the tolerability of osimertinib by identifying its toxic limit
No full textSupplemental material, sj-docx-1-tam-10.1177_17588359221103212 for Improving the tolerability of osimertinib by identifying its toxic limit by Bram C. Agema, G. D. Marijn Veerman, Christi M. J. Steendam, Daan A. C. Lanser, Tim Preijers, Cor van der Leest, Birgit C. P. Koch, Anne-Marie C. Dingemans, Ron H. J. Mathijssen and Stijn L. W. Koolen in Therapeutic Advances in Medical Oncology</p
Factors affecting inter-individual variability in endoxifen concentrations in patients with breast cancer : results from the prospective TOTAM trial
Get PDFAbstract: Introduction Endoxifen-the principal metabolite of tamoxifen-is subject to a high inter-individual variability in serum concentration. Numerous attempts have been made to explain this, but thus far only with limited success. By applying predictive modeling, we aimed to identify factors that determine the inter-individual variability. Our purpose was to develop a prediction model for endoxifen concentrations, as a strategy to individualize tamoxifen treatment by model-informed dosing in order to prevent subtherapeutic exposure (endoxifen < 16 nmol/L) and thus potential failure of therapy. Methods Tamoxifen pharmacokinetics with demographic and pharmacogenetic data of 303 participants of the prospective TOTAM study were used. The inter-individual variability in endoxifen was analyzed according to multiple regression techniques in combination with multiple imputations to adjust for missing data and bootstrapping to adjust for the over-optimism of parameter estimates used for internal model validation. Results Key predictors of endoxifen concentration were CYP2D6 genotype, age and weight, explaining altogether an average-based optimism corrected 57% (95% CI 0.49-0.64) of the inter-individual variability. CYP2D6 genotype explained 54% of the variability. The remaining 3% could be explained by age and weight. Predictors of risk for subtherapeutic endoxifen (< 16 nmol/L) were CYP2D6 genotype and age. The model showed an optimism-corrected discrimination of 90% (95% CI 0.86-0.95) and sensitivity and specificity of 66% and 98%, respectively. Consecutively, there is a high probability of misclassifying patients with subtherapeutic endoxifen concentrations based on the prediction rule. Conclusion The inter-individual variability of endoxifen concentration could largely be explained by CYP2D6 genotype and for a small proportion by age and weight. The model showed a sensitivity and specificity of 66 and 98%, respectively, indicating a high probability of (misclassification) error for the patients with subtherapeutic endoxifen concentrations (< 16 nmol/L). The remaining unexplained inter-individual variability is still high and therefore model-informed tamoxifen dosing should be accompanied by therapeutic drug monitoring
Design of microcavity resonators for single-atom detection
Get PDFWhispering gallery modes of a microdisk resonator are useful for the optical detection of single rubidium and cesium atoms near the surface of a substrate. Light is coupled into two high-Q whispering-gallery modes of the disk which can provide attractive and/or repulsive potentials, respectively, via their evanescent fields. The sum potential, including van der Waals/Casimir-Polder surface forces, may be tuned to exhibit a minimum at distances on the order of 100nm from the disk surface. Simultaneously optically trapping and detecting is possible, with the back-action of an atom held in this trap on the light fields being sufficiently strong to provide a measurable effect. Atom trapping and detection depend on a variety of system parameters and experimental realizations differ for different atoms
Sports Fans' Evaluations of Sporting Code Innovations
No full textToday's professional sports are frequently evolving and changing their design, structure and format. Many such innovations have been spurred on by the opportunity to capitalise financially on new markets and increase profit. This study used both quantitative (survey) and qualitative (depth interviews) methods in order to examine fans' attitudes towards the current state of Rugby Union, Rugby League, Netball, Soccer and Cricket. The findings for Rugby Union concluded that the recent experimental law variations have succeeded in what they were introduced to do. Fans believe that Rugby is more exciting to watch than ever before and that it is now a faster and more attack-focused contest. Fans believe that Rugby League has improved following the introduction of the video referee and in particular by the use of two on-field referees. They believe that it is now a more exciting and faster game. Fans also believe that salary caps are good for Rugby League and help to increase competition and spread the wealth of talent among the teams. Netball fans are excited by possible new innovations and show support for the inclusion of power plays, two point goals, rolling substitutions and increased physical contact. Fans believe that Soccer needs to adopt technology in order to help its officials but they also admire the traditionalism of the code. Surprisingly, fans show support for increasing the sizes of Soccer‟s goals in order to make it easier for teams to score. Fans show support for Twenty20 cricket and seem undeterred by recent match fixing scandals. There is also evident support for the introduction of Beach Cricket to New Zealand. Analysing fans' attitudes towards professional sport's product innovations has led to a final implication and conclusion for the administrators and governing bodies of professional sport. That is, it would be wise to keep the traditional codes and their formats as traditional as possible. However, evolve the same sport in to a completely separate format in order to financially capitalise on different markets. Twenty20 cricket is a perfect example of this
Acute Ethanol Administration Rapidly Increases Phosphorylation of Conventional Protein Kinase C in Specific Mammalian Brain Regions in Vivo
Get PDFBackground
Protein kinase C (PKC) is a family of isoenzymes that regulate a variety of functions in the central nervous system including neurotransmitter release, ion channel activity, and cell differentiation. Growing evidence suggests that specific isoforms of PKC influence a variety of behavioral, biochemical, and physiological effects of ethanol in mammals. The purpose of this study was to determine whether acute ethanol exposure alters phosphorylation of conventional PKC isoforms at a threonine 674 (p-cPKC) site in the hydrophobic domain of the kinase, which is required for its catalytic activity.
Methods
Male rats were administered a dose range of ethanol (0, 0.5, 1, or 2 g/kg, intragastric) and brain tissue was removed 10 minutes later for evaluation of changes in p-cPKC expression using immunohistochemistry and Western blot methods.
Results
Immunohistochemical data show that the highest dose of ethanol (2 g/kg) rapidly increases p-cPKC immunoreactivity specifically in the nucleus accumbens (core and shell), lateral septum, and hippocampus (CA3 and dentate gyrus). Western blot analysis further showed that ethanol (2 g/kg) increased p-cPKC expression in the P2 membrane fraction of tissue from the nucleus accumbens and hippocampus. Although p-cPKC was expressed in numerous other brain regions, including the caudate nucleus, amygdala, and cortex, no changes were observed in response to acute ethanol. Total PKC? immunoreactivity was surveyed throughout the brain and showed no change following acute ethanol injection
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