99 research outputs found
Feasibility of a 12-month-exercise intervention during and after radiation and chemotherapy in cancer patients: impact on quality of life, peak oxygen consumption, and body composition
Polymorphisms in the multiple drug resistance protein 1 and in P-glycoprotein 1 are associated with time to event outcomes in patients with advanced multiple myeloma treated with bortezomib and pegylated liposomal doxorubicin
Single nucleotide polymorphisms (SNPs) in the multiple drug resistance protein 1 (MRP1) and P-glycoprotein 1 (MDR1) genes modulate their ability to mediate drug resistance. We therefore sought to retrospectively evaluate their influence on outcomes in relapsed and/or refractory myeloma patients treated with bortezomib or bortezomib with pegylated liposomal doxorubicin (PLD). The MRP1/R723Q polymorphism was found in five subjects among the 279 patient study population, all of whom received PLDâ+âbortezomib. Its presence was associated with a longer time to progression (TTP; median 330 vs. 129Â days; pâ=â0.0008), progression-free survival (PFS; median 338 vs. 129Â days; pâ=â0.0006), and overall survival (pâ=â0.0045). MDR1/3435(Câ>âT), which was in HardyâWeinberg equilibrium, showed a trend of association with PFS (pâ=â0.0578), response rate (pâ=â0.0782) and TTP (pâ=â0.0923) in PLDâ+âbortezomib patients, though no correlation was found in the bortezomib arm. In a recessive genetic model, MDR1/3435Â T was significantly associated with a better TTP (pâ=â0.0405) and PFS (pâ=â0.0186) in PLDâ+âbortezomib patients. These findings suggest a potential role for MRP1 and MDR1 SNPs in modulating the long-term outcome of relapsed and/or refractory myeloma patients treated with PLDâ+âbortezomib. Moreover, they support prospective studies to determine if such data could be used to tailor therapy to the genetic makeup of individual patients
Resistance reversal by RNAi silencing of MDR1 in CML cells associated with increase in imatinib intracellular levels.
siRNA-Mediated Knock-Down of P-Glycoprotein Expression Reveals Distinct Cellular Disposition of Anticancer Tyrosine Kinases Inhibitors.
Studies on the cellular disposition of targeted anticancer tyrosine kinases inhibitors (TKIs) have mostly focused on imatinib while the functional importance of P-glycoprotein (Pgp) the gene product of MDR1 remains controversial for more recent TKIs. By using RNA interference-mediated knockdown of MDR1, we have investigated and compared the specific functional consequence of Pgp on the cellular disposition of the major clinically in use TKIs imatinib, dasatinib, nilotinib, sunitinib and sorafenib. siRNA-mediated knockdown in K562/Dox cell lines provides a unique opportunity to dissect the specific contribution of Pgp to TKIs intracellular disposition. In these conditions, abrogating specifically Pgp-mediated efflux in vitro revealed the remarkable and statistically significant cellular accumulation of imatinib (difference in cellular levels between Pgp-expressing and silenced cells, at high and low incubation concentration, respectively: 6.1 and 6.6), dasatinib (4.9 and 5.6), sunitinib (3.7 and 7.3) and sorafenib (1.2 and 1.4), confirming that these TKIs are all substrates of Pgp. By contrast, no statistically significant difference in cellular disposition of nilotinib was observed as a result of MDR1 expression silencing (differences: 1.1 and 1.5) indicating that differential expression and/or function of Pgp is unlikely to affect nilotinib cellular disposition. This study enables for the first time a direct estimation of the specific contribution of one transporter among the various efflux and influx carriers involved in the cellular trafficking of these major TKIs in vitro. Knowledge on the distinct functional consequence of Pgp expression for these various TKIs cellular distribution is necessary to better appreciate the efficacy, toxicity, and potential drug-drug interactions of TKIs with other classes of therapeutic agents, at the systemic, tissular and cellular levels
Power to the voice hearer - The German version of the voice power differential scale.
Voice power is an important concept in daily life of voice hearers and in the support and therapy for voice hearers who seek help. Therefore, the ability to examine voice power differentials between a voice and a voice hearer is essential. The present study aimed to collect data on voice power differentials and to further validate the Voice Power Differential Scale (VPD). 105 participants aged â„ 18 with an ICD10 F2-diagnosis that included hearing voices were included in this study. Internal consistency was good (alpha = 0.792), as well as test-retest-reliability (r = 0.855) and correlations with other constructs were generally as expected. The VPD questionnaire results correlated negatively with the Beliefs About Voices Questionnaire-Revised's (BAVQ-R) items of Benevolence and Engagement-emotion. It correlated positively with Omnipotence and Resistance-emotion, as well as with Negative Content on the Psychotic Symptoms Rating-Scale (PSYRATS). Unexpectedly, no correlations were found with overall severity and command hallucinations. The Voice Power Differential Scale is an important tool for assessing and formulating a voice hearer's experience when they seek treatment or support for their verbal auditory hallucinations. The results of this study enrich the on-going discussion about the importance of voice power for voice hearers
Patients with a deficiency of natural killer cell activity lack the VEP13-positive lymphocyte subpopulation
Implementing a novel online education programme to support RTQA - the EMBRACE-II experience
Biological, physical and clinical aspects of cancer treatment with ionising radiatio
Abhaltung und Evaluierung einer Ringvorlesung zum Thema "Gender-Unterschiede in der OrthopĂ€die" an der Medizinischen UniversitĂ€t Graz als Beispiel fĂŒr fachspezifische Implementierung von Gender-Medizin in der universitĂ€ren Lehre
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