Karen Williams | Independent Researcher (original) (raw)
Papers by Karen Williams
Molecular Cancer Therapeutics, 2013
Although mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK)... more Although mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition is predicted to cause cell death by stabilization of the proapoptotic BH3-only protein BIM, the induction of apoptosis is often modest. To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor, we evaluated a panel of 53 non–small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax (ABT-263), a Bcl-2/Bcl-xL (BCL2/BCL2L1) antagonist, and a novel MAP kinase (MEK) inhibitor, G-963. The combination is synergistic in the majority of lines, with an enrichment of cell lines harboring KRAS mutations in the high synergy group. Cells exposed to G-963 arrest in G1 and a small fraction undergo apoptosis. The addition of navitoclax to G-963 does not alter the kinetics of cell-cycle arrest, but greatly increases the percentage of cells that undergo apoptosis. The G-963/navitoclax combination was more effective than...
Medicine & Science in Sports & Exercise, 2009
Medicine & Science in Sports & Exercise, 2010
Purpose: To examine alterations in muscle contractile properties, cortical excitability, and volu... more Purpose: To examine alterations in muscle contractile properties, cortical excitability, and voluntary activation as a consequence of 20 d of repetitive endurance cycling within a 22-d period. Methods: Eight well-trained male cyclists completed 20 prolonged cycling stages interspersed by two rest days (days 9 and 17), which replicated the 2007 Tour de France route and schedule. Isometric knee extensor torque and EMG responses of the vastus lateralis in response to percutaneous electrical stimulation and transcranial magnetic stimulation were measured before, on days 9 and 17, and 2 d after completion of Tour de France. Postexercise measurements on days 9 and 17 were taken 918 h after cessation of the previous exercise bout. Results: Maximal voluntary contraction of the knee extensors decreased by 20 T 10% (P G 0.01) during Tour de France but recovered after 2 d of rest. Peripherally evoked M-wave and potentiated twitch responses were also significantly decreased during Tour de France, up to 31 T 21% and 22 T 18%, respectively (P G 0.05), but returned to baseline values after 2 d of recovery. Voluntary activation was reduced to 75 T 8% (P G 0.05) during Tour de France and remained significantly depressed (79 T 7%, P G 0.05) after completion. The amplitude of motor evoked potentials was decreased by 44 T 28% (P G 0.01) on day 9 and remained significantly depressed during the remainder of, and after, Tour de France. Conclusions: A reduction in knee extensor strength, which occurs after repetitive prolonged cycling exercise, is a result of both central and peripheral processes. Reduced sarcolemmal excitability and impairment of contractile mechanisms exists even after 18 h of recovery. An enduring reduction in corticomotor output persists even after 2 d of rest.
Journal of the American College of Cardiology, 2011
Journal of Prosthodontics, 2007
Journal of Prosthodontics, 2005
Circulation: Cardiovascular Imaging, 2011
Background— Running an ultramarathon has been shown to have a transient negative effect on right ... more Background— Running an ultramarathon has been shown to have a transient negative effect on right ventricular (RV) and left ventricular (LV) function. Additionally, recent findings suggested that ultraendurance athletes may be more at risk of developing a RV cardiomyopathy. The standard echocardiographic assessment of RV function is problematic; however, the introduction of ultrasonic speckle tracking technology has the potential to yield a comprehensive evaluation of RV longitudinal function, providing new insights into this phenomenon. Thus, the primary aim of this exploratory study was to evaluate comprehensively RV structure and function after a 161-km ultramarathon and establish whether changes in the RV are associated with alterations in LV function. Methods and Results— Myocardial speckle tracking echocardiograms of the RV and LV were obtained before and immediately after a 161-km ultramarathon in 16 healthy adults. Standard echocardiography was used to determine RV size and f...
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](Bioorganic & Medicinal Chemistry Letters, 2008
Bioorganic & Medicinal Chemistry Letters, 2007
Molecular Cancer Therapeutics, 2013
Although mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK)... more Although mitogen-activated protein (MAP)–extracellular signal-regulated kinase (ERK) kinase (MEK) inhibition is predicted to cause cell death by stabilization of the proapoptotic BH3-only protein BIM, the induction of apoptosis is often modest. To determine if addition of a Bcl-2 family inhibitor could increase the efficacy of a MEK inhibitor, we evaluated a panel of 53 non–small cell lung cancer and pancreatic cancer cell lines with the combination of navitoclax (ABT-263), a Bcl-2/Bcl-xL (BCL2/BCL2L1) antagonist, and a novel MAP kinase (MEK) inhibitor, G-963. The combination is synergistic in the majority of lines, with an enrichment of cell lines harboring KRAS mutations in the high synergy group. Cells exposed to G-963 arrest in G1 and a small fraction undergo apoptosis. The addition of navitoclax to G-963 does not alter the kinetics of cell-cycle arrest, but greatly increases the percentage of cells that undergo apoptosis. The G-963/navitoclax combination was more effective than...
Medicine & Science in Sports & Exercise, 2009
Medicine & Science in Sports & Exercise, 2010
Purpose: To examine alterations in muscle contractile properties, cortical excitability, and volu... more Purpose: To examine alterations in muscle contractile properties, cortical excitability, and voluntary activation as a consequence of 20 d of repetitive endurance cycling within a 22-d period. Methods: Eight well-trained male cyclists completed 20 prolonged cycling stages interspersed by two rest days (days 9 and 17), which replicated the 2007 Tour de France route and schedule. Isometric knee extensor torque and EMG responses of the vastus lateralis in response to percutaneous electrical stimulation and transcranial magnetic stimulation were measured before, on days 9 and 17, and 2 d after completion of Tour de France. Postexercise measurements on days 9 and 17 were taken 918 h after cessation of the previous exercise bout. Results: Maximal voluntary contraction of the knee extensors decreased by 20 T 10% (P G 0.01) during Tour de France but recovered after 2 d of rest. Peripherally evoked M-wave and potentiated twitch responses were also significantly decreased during Tour de France, up to 31 T 21% and 22 T 18%, respectively (P G 0.05), but returned to baseline values after 2 d of recovery. Voluntary activation was reduced to 75 T 8% (P G 0.05) during Tour de France and remained significantly depressed (79 T 7%, P G 0.05) after completion. The amplitude of motor evoked potentials was decreased by 44 T 28% (P G 0.01) on day 9 and remained significantly depressed during the remainder of, and after, Tour de France. Conclusions: A reduction in knee extensor strength, which occurs after repetitive prolonged cycling exercise, is a result of both central and peripheral processes. Reduced sarcolemmal excitability and impairment of contractile mechanisms exists even after 18 h of recovery. An enduring reduction in corticomotor output persists even after 2 d of rest.
Journal of the American College of Cardiology, 2011
Journal of Prosthodontics, 2007
Journal of Prosthodontics, 2005
Circulation: Cardiovascular Imaging, 2011
Background— Running an ultramarathon has been shown to have a transient negative effect on right ... more Background— Running an ultramarathon has been shown to have a transient negative effect on right ventricular (RV) and left ventricular (LV) function. Additionally, recent findings suggested that ultraendurance athletes may be more at risk of developing a RV cardiomyopathy. The standard echocardiographic assessment of RV function is problematic; however, the introduction of ultrasonic speckle tracking technology has the potential to yield a comprehensive evaluation of RV longitudinal function, providing new insights into this phenomenon. Thus, the primary aim of this exploratory study was to evaluate comprehensively RV structure and function after a 161-km ultramarathon and establish whether changes in the RV are associated with alterations in LV function. Methods and Results— Myocardial speckle tracking echocardiograms of the RV and LV were obtained before and immediately after a 161-km ultramarathon in 16 healthy adults. Standard echocardiography was used to determine RV size and f...
Bioorganic & Medicinal Chemistry Letters, 2008
Bioorganic & Medicinal Chemistry Letters, 2007