| 1. |
|
|
| 2. |
|
|
| 3. |
- Zamora, Juan Carlos, et al.
(författare)
-
Considerations and consequences of allowing DNA sequence data as types of fungal taxa
- 2018
-
Ingår i: IMA Fungus. - : INT MYCOLOGICAL ASSOC. - 2210-6340 .- 2210-6359. ; 9:1, s. 167-185
-
Tidskriftsartikel (refereegranskat)abstract
- Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.
|
|
| 4. |
- Duarte-Salles, Talita, et al.
(författare)
-
Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort
- 2015
-
Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 137:11, s. 2715-2728
-
Tidskriftsartikel (refereegranskat)abstract
- The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, which includes 191 incident HCC cases diagnosed between 1992 and 2010. Diet was assessed by country-specific, validated dietary questionnaires. A single 24-hr diet recall from a cohort subsample was used for measurement error calibration. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated from Cox proportional hazard models. Hepatitis B and C viruses (HBV/HCV) status and biomarkers of liver function were assessed separately in a nested case-control subset with available blood samples (HCC = 122). In multivariable calibrated models, there was a statistically significant inverse association between total fat intake and risk of HCC (per 10 g/day, HR = 0.80, 95% CI: 0.65-0.99), which was mainly driven by monounsaturated fats (per 5 g/day, HR = 0.71, 95% CI: 0.55-0.92) rather than polyunsaturated fats (per 5 g/day, HR = 0.92, 95% CI: 0.68-1.25). There was no association between saturated fats (HR = 1.08, 95% CI: 0.88-1.34) and HCC risk. The ratio of polyunsaturated/monounsaturated fats to saturated fats was not significantly associated with HCC risk (per 0.2 point, HR = 0.86, 95% CI: 0.73-1.01). Restriction of analyses to HBV/HCV free participants or adjustment for liver function did not substantially alter the findings. In this large prospective European cohort, higher consumption of monounsaturated fats is associated with lower HCC risk.
|
|
| 5. |
- Edhborg, Fredrik, 1990, et al.
(författare)
-
Triplet States of Cyanostar and Its Anion Complexes
- 2023
-
Ingår i: Journal of Physical Chemistry A. - 1089-5639 .- 1520-5215. ; 127:28, s. 5841-5850
-
Tidskriftsartikel (refereegranskat)abstract
- The design of advanced optical materials based on triplet states requires knowledge of the triplet energies of the molecular building blocks. To this end, we report the triplet energy of cyanostar (CS) macrocycles, which are the key structure-directing units of small-molecule ionic isolation lattices (SMILES) that have emerged as programmable optical materials. Cyanostar is a cyclic pentamer of covalently linked cyanostilbene units that form π-stacked dimers when binding anions as 2:1 complexes. The triplet energies, ET, of the parent cyanostar and its 2:1 complex around PF6- are measured to be 1.96 and 2.02 eV, respectively, using phosphorescence quenching studies at room temperature. The similarity of these triplet energies suggests that anion complexation leaves the triplet energy relatively unchanged. Similar energies (2.0 and 1.98 eV, respectively) were also obtained from phosphorescence spectra of the iodinated form, I-CS, and of complexes formed with PF6- and IO4- recorded at 85 K in an organic glass. Thus, measures of the triplet energies likely reflect geometries close to those of the ground state either directly by triplet energy transfer to the ground state or indirectly by using frozen media to inhibit relaxation. Density functional theory (DFT) and time-dependent DFT were undertaken on a cyanostar analogue, CSH, to examine the triplet state. The triplet excitation localizes on a single olefin whether in the single cyanostar or its π-stacked dimer. Restriction of the geometrical changes by forming either a dimer of macrocycles, (CSH)2, or a complex, (CSH)2·PF6-, reduces the relaxation resulting in an adiabatic energy of the triplet state of 2.0 eV. This structural constraint is also expected for solid-state SMILES materials. The obtained T1 energy of 2.0 eV is a key guide line for the design of SMILES materials for the manipulation of triplet excitons by triplet state engineering in the future.
|
|
| 6. |
- Guaita, Lucia, et al.
(författare)
-
The Lyman alpha reference sample IV. Morphology at low and high redshift
- 2015
-
Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 576
-
Tidskriftsartikel (refereegranskat)abstract
- Context. The transport of Ly alpha photons in galaxies is a complex process and the conditions under which Ly alpha photons manage to escape from certain galaxies is still under investigation. The Lyman alpha reference sample (LARS) is a sample of 14 local star-forming galaxies, designed to study Ly alpha in detail and relate it to rest-frame UV and optical emission. Aims. With the aim of identifying rest-frame UV and optical properties, which are typical of Ly alpha emitters (LAEs, galaxies with EW(Ly alpha) > 20 angstrom) at both low and high redshift, we investigated the morphological properties of the LARS galaxies, in particular the ones that exhibit intense Ly alpha radiation. Methods. We measured sizes and morphological parameters in the continuum, Ly alpha, and Ha images. We studied morphology by using the Gini coefficient vs. M20 and asymmetry vs. concentration diagrams. We then simulated LARS galaxies at z similar to 2 and 5.7, performing the same morphological measurements. We also investigated the detectability of LARS galaxies in current deep field observations. The subsample of LAEs within LARS (LARS-LAEs) was stacked to provide a comparison to stacking studies performed at high redshift. Results. LARS galaxies have continuum size, stellar mass, and rest-frame absolute magnitude typical of Lyman break analogues in the local Universe and also similar to 2 < z < 3 star-forming galaxies and massive LAEs. LARS optical morphology is consistent with the one of merging systems, and irregular or starburst galaxies. For the first time we quantify the morphology in Ly alpha images: even if a variety of intrinsic conditions of the interstellar medium can favour the escape of Ly alpha photons, LARS-LAEs appear small in the continuum, and their Ly alpha is compact. LARS galaxies tend to be more extended in Ly alpha than in the rest-frame UV. It means that Ly alpha photons escape by forming haloes around HII regions of LARS galaxies. Conclusions. The stack of LARS-LAE Ly alpha images is peaked in the centre, indicating that the conditions, which make a galaxy an LAE, tend to produce a concentrated surface brightness profile. On the other hand, the stack of all LARS galaxies is shallower and more extended. This can be caused by the variety of dust and HI amount and distribution, which produces a more complex, patchy, and extended profile, like the one observed for Lyman break galaxies that can contribute to the stack. We cannot identify a single morphological property that controls whether a galaxy emits a net positive Ly alpha flux. However, the LARS-LAEs have continuum properties consistent with merging systems.
|
|
| 7. |
- Laursen, K. R., et al.
(författare)
-
An RCT of acute health effects in COPD-patients after passive vape exposure from e-cigarettes
- 2021
-
Ingår i: European Clinical Respiratory Journal. - : Informa UK Limited. - 2001-8525. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: E-cigarette use has been shown to have short-term acute effects among active users but less is known of the acute passive effects, particularly among individuals with existing respiratory diseases. Objective: To investigate local and systemic effects of short-term passive vape exposure among patients with mild or moderate chronic obstructive pulmonary disease (COPD). Methods: In a double-blinded crossover study 16 non-smoking COPD-patients (mean age 68) were randomly exposed for 4 h to passive vape (median PM2.5: 18 mu g/m(3) (range: 8-333)) and clean air (PM2.5 < 6 mu g/m(3)) separated by 14 days. Particles were measured using an ultrafine particle counter (P-TRAK) and a scanning mobility particle sizer (SMPS). Health effects including Surfactant Protein-A (SP-A) and albumin in exhaled air, spirometry, FeNO, and plasma proteins were evaluated before, right after, and 24 hours after exposure. Participants reported symptoms throughout exposure sessions. Data were analyzed using mixed models. Results: SP-A in exhaled air was negatively affected by exposure to vape and several plasma proteins increased significantly. Throat irritation was more pronounced during passive vape exposure, while FVC and FEV1 decreased, however, not significantly. Conclusions: SP-A in exhaled air and some plasma proteins were affected by passive vape in patients with COPD indicating inflammation, showing that passive vape exposure is potentially harmful.
|
|
| 8. |
- Lund, M. V., et al.
(författare)
-
Beta-delayed proton emission from 21Mg
- 2015
-
Ingår i: European Physical Journal A. - : Springer Science and Business Media LLC. - 1434-601X .- 1434-6001. ; 51:9, s. Art. no. 113-
-
Tidskriftsartikel (refereegranskat)abstract
- Beta-delayed proton emission from 21Mg has been measured at ISOLDE, CERN, with a detection setup consisting of two charged-particle telescopes surrounding the decay point. Altogether 27 βp branches were measured with center-of-mass energies between 0.4–7.2 MeV. Seven new βp branches were observed. Beta-delayed protons were used to determine the half-life of 21Mg as 118.6 ± 0.5 ms. From a line shape fit of the βp branches we extract the widths, spins, and parities of the resonances of 21Na. An improved interpretation of the decay scheme in accordance with the results obtained in reaction studies is presented.
|
|
| 9. |
- Lund, M. V., et al.
(författare)
-
Systematic trends in beta-delayed particle emitting nuclei: The case of beta p alpha emission from Mg-21
- 2015
-
Ingår i: Physics Letters. Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 750, s. 356-359
-
Tidskriftsartikel (refereegranskat)abstract
- We have observed beta(+)-delayed alpha and p alpha emission from the proton-rich nucleus Mg-21 produced at the ISOLDE facility at CERN. The assignments were cross-checked with a time distribution analysis. This is the third identified case of beta p alpha emission. We discuss the systematic of beta-delayed particle emission decays, show that our observed decays fit naturally into the existing pattern, and argue that the patterns are to a large extent caused by odd-even effects. (C) 2015 The Authors. Published by Elsevier B.V.
|
|
| 10. |
- Lund, M. V., et al.
(författare)
-
Systematic trends in beta-delayed particle emitting nuclei: The case of βpα emission from 21Mg
- 2015
-
Ingår i: Physics Letters, Section B: Nuclear, Elementary Particle and High-Energy Physics. - : Elsevier BV. - 0370-2693. ; 750:Art. no. 31347, s. 356-359
-
Tidskriftsartikel (refereegranskat)abstract
- We have observed β+-delayed α and pα emission from the proton-rich nucleus 21Mg produced at the ISOLDE facility at CERN. The assignments were cross-checked with a time distribution analysis. This is the third identified case of βpα emission. We discuss the systematic of beta-delayed particle emission decays, show that our observed decays fit naturally into the existing pattern, and argue that the patterns are to a large extent caused by odd-even effects.
|
|
| 11. |
- Tolsgaard, Martin G., et al.
(författare)
-
The effect of constructing versus solving virtual patient cases on transfer of learning : a randomized trial
- 2016
-
Ingår i: Perspectives on Medical Education. - : Ubiquity Press, Ltd.. - 2212-277X. ; 5:1, s. 33-38
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to explore the effect of actively constructing virtual patient (VP) cases compared with solving VP cases on knowledge gains, skills transfer and time spent on cases. Forty-five fourth-year medical students were randomized to constructing (VP-construction, n = 23) or solving (VP-solving, n = 22) four cardiopulmonary VP cases. Whereas the VP-solving group solved the cases, the VP-construction group only received the final diagnosis and had to complete the history, physical findings, and lab results. After a week, participants completed a transfer test involving two standardized patients representing cardiopulmonary cases. Performances on the transfer test were video-recorded and assessed by two blinded raters using the Reporter, Interpreter, Manager, Educator (RIME) framework. Thirty-nine participants completed the transfer test. The VP-construction group spent significantly more time on the VP cases compared with the VP-solving group, p = 0.002. There were no significant differences in RIME scores between the VP-construction group and VP-solving group, p = 0.54.In conclusion, engaging novice students in active VP case construction may be more time consuming than solving VP cases, without resulting in superior skills transfer.
|
|
| 12. |
- Bagga-Gupta, Sangeeta, 1962-, et al.
(författare)
-
Preface
- 2019
-
Ingår i: Reconceptualizing connections between language, literacy and learning. - : Springer. - 9783030269937 ; , s. v-vi
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 13. |
- Brennan, D. J., et al.
(författare)
-
The cocaine- and amphetamine-regulated transcript mediates ligand-independent activation of ER alpha, and is an independent prognostic factor in node-negative breast cancer
- 2012
-
Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:30, s. 3483-3494
-
Tidskriftsartikel (refereegranskat)abstract
- Personalized medicine requires the identification of unambiguous prognostic and predictive biomarkers to inform therapeutic decisions. Within this context, the management of lymph node-negative breast cancer is the subject of much debate with particular emphasis on the requirement for adjuvant chemotherapy. The identification of prognostic and predictive biomarkers in this group of patients is crucial. Here, we demonstrate by tissue microarray and automated image analysis that the cocaine- and amphetamine-regulated transcript (CART) is expressed in primary and metastatic breast cancer and is an independent poor prognostic factor in estrogen receptor (ER)-positive, lymph node-negative tumors in two separate breast cancer cohorts (n = 690; P = 0.002, 0.013). We also show that CART increases the transcriptional activity of ER alpha in a ligand-independent manner via the mitogen-activated protein kinase pathway and that CART stimulates an autocrine/paracrine loop within tumor cells to amplify the CART signal. Additionally, we demonstrate that CART expression in ER-positive breast cancer cell lines protects against tamoxifen-mediated cell death and that high CART expression predicts disease outcome in tamoxifen-treated patients in vivo in three independent breast cancer cohorts. We believe that CART profiling will help facilitate stratification of lymph node-negative breast cancer patients into high- and low-risk categories and allow for the personalization of therapy. Oncogene (2012) 31, 3483-3494; doi:10.1038/onc.2011.519; published online 5 December 2011
|
|
| 14. |
|
|
| 15. |
- Dalgard, O., et al.
(författare)
-
Sofosbuvir based treatment of chronic hepatitis C genotype 3 infections-A Scandinavian real-life study
- 2017
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:7
-
Tidskriftsartikel (refereegranskat)abstract
- Background and aims Chronic hepatitis C virus (HCV) genotype 3 infection with advanced liver disease has emerged as the most challenging to treat. We retrospectively assessed the treatment outcome of sofosbuvir (SOF) based regimes for treatment of HCV genotype 3 infections in a real life setting in Scandinavia. Methods Consecutive patients with chronic HCV genotype 3 infection were enrolled at 16 treatment centers in Denmark, Sweden, Norway and Finland. Patients who had received a SOF containing regimen were included. The fibrosis stage was evaluated by liver biopsy or transient liver elastography. The following treatments were given according availability and local guidelines: 1) SOF + ribavirin (RBV) for 24 weeks, 2) SOF + daclatasvir (DCV) +/-RBV for 12-24 weeks, 3) SOF + pegylated interferon alpha (peg-IFN-a) + RBV for 12 weeks or 4) SOF/ledipasvir (LDV) + RBV for 12-16 weeks. The primary endpoint was sustained virological response (SVR) assessed at week 12 (SVR12) after end of treatment. Results We included 316 patients with a mean age of 55 years (range 24-79), 70% men, 49% treatment experienced, 58% with compensated cirrhosis and 12% with decompensated cirrhosis. In the modified intention to treat (mITT) population SVR12 was achieved in 284/311 91%) patients. Among 26 treatment failures, five had non-response, 3 breakthrough and 18 relapse. Five patients were not included in the mITT population. Three patients died from reasons unrelated to treatment and two were lost to follow-up. The SVR12 rate was similar for all treatment regimens, but lower in men (p = 0.042), and in patients with decompensated liver disease (p = 0.004). Conclusion We found that sofosbuvir based treatment in a real-life setting could offer SVR rates exceeding 90% in patients with HCV genotype 3 infection and advanced liver disease.
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
- Galea, V. P., et al.
(författare)
-
Evaluation of in vivo wear of vitamin E-diffused highly crosslinked polyethylene at five years
- 2018
-
Ingår i: Bone and Joint Journal. - 2049-4394. ; 100B100-B:12, s. 1592-1599
-
Tidskriftsartikel (refereegranskat)abstract
- Aims The primary aim of this study was to compare the wear properties of vitamin E-diffused, highly crosslinked polyethylene (VEPE) and one formulation of moderately crosslinked and mechanically annealed ultra-high molecular weight polyethylene (ModXLPE) in patients five years after primary total hip arthroplasty (THA). The secondary aim was to assess the clinical results of patients treated with VEPE by evaluating patient-reported outcome measures (PROMs), radiological evidence of fixation, and the incidence of mechanical failure. Patients and Methods A total of 208 patients (221 THAs) from four international centres were recruited into a prospective study involving radiostereometric analysis (RSA) and the assessment of clinical outcomes. A total of 193 hips (87%) were reviewed at the five-year follow-up. Of these, 136 (70%) received VEPE (vs ModXLPE) liners and 68 (35%) received ceramic (vs metal) femoral heads. PROMs and radiographs were collected preoperatively and at one, two, and five years postoperatively. In addition, RSA images were collected to measure PE wear postoperatively and at one, two, and five years after surgery. Results We observed similar bedding in one year postoperatively and wear two years postoperatively between the two types of liner. However, there was significantly more penetration of the femoral head in the ModXLPE cohort compared with the VEPE cohort five years postoperatively (p < 0.001). The only variables independently predictive of increased wear were ModXLPE (vs VEPE) liner type (β = 0.22, p = 0.010) and metal (vs ceramic) femoral head (β = 0.21, p = 0.013). There was no association between increased wear and the development of radiolucency (p = 0.866) or PROMs. No patient had evidence of osteolysis. Conclusion Five years postoperatively, patients with VEPE (vs ModXLPE) and ceramic (vs metal) femoral heads had decreased wear. The rates of wear for both liners were very low and have not led to any osteolysis or implant failure due to aseptic loosening. ©2018 The British Editorial Society of Bone & Joint Surgery.
|
|
| 22. |
- Grunddal, K. V., et al.
(författare)
-
Opposing roles of the entero-pancreatic hormone urocortin-3 in glucose metabolism in rats
- 2022
-
Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 65, s. 1018-1031
-
Tidskriftsartikel (refereegranskat)abstract
- Aim/hypothesis Urocortin-3 (UCN3) is a glucoregulatory peptide produced in the gut and pancreatic islets. The aim of this study was to clarify the acute effects of UCN3 on glucose regulation following an oral glucose challenge and to investigate the mechanisms involved. Methods We studied the effect of UCN3 on blood glucose, gastric emptying, glucose absorption and secretion of gut and pancreatic hormones in male rats. To supplement these physiological studies, we mapped the expression of UCN3 and the UCN3-sensitive receptor, type 2 corticotropin-releasing factor receptor (CRHR2), by means of fluorescence in situ hybridisation and by gene expression analysis. Results In rats, s.c. administration of UCN3 strongly inhibited gastric emptying and glucose absorption after oral administration of glucose. Direct inhibition of gastrointestinal motility may be responsible because UCN3's cognate receptor, CRHR2, was detected in gastric submucosal plexus and in interstitial cells of Cajal. Despite inhibited glucose absorption, post-challenge blood glucose levels matched those of rats given vehicle in the low-dose UCN3 group, because UCN3 concomitantly inhibited insulin secretion. Higher UCN3 doses did not further inhibit gastric emptying, but the insulin inhibition progressed resulting in elevated post-challenge glucose and lipolysis. Incretin hormones and somatostatin (SST) secretion from isolated perfused rat small intestine was unaffected by UCN3 infusion; however, UCN3 infusion stimulated secretion of somatostatin from delta cells in the isolated perfused rat pancreas which, unlike alpha cells and beta cells, expressed Crhr2. Conversely, acute antagonism of CRHR2 signalling increased insulin secretion by reducing SST signalling. Consistent with these observations, acute drug-induced inhibition of CRHR2 signalling improved glucose tolerance in rats to a similar degree as administration of glucagon-like peptide-1. UCN3 also powerfully inhibited glucagon secretion from isolated perfused rat pancreas (perfused with 3.5 mmol/l glucose) in a SST-dependent manner, suggesting that UCN3 may be involved in glucose-induced inhibition of glucagon secretion. Conclusions/interpretation Our combined data indicate that UCN3 is an important glucoregulatory hormone that acts through regulation of gastrointestinal and pancreatic functions.
|
|
| 23. |
|
|
| 24. |
- Kjaer, Christina, et al.
(författare)
-
Luminescence Spectroscopy of Rhodamine Homodimer Dications in Vacuo Reveals Strong Dye-Dye Interactions
- 2019
-
Ingår i: ChemPhysChem. - : Wiley. - 1439-4235 .- 1439-7641. ; 20:4, s. 533-537
-
Tidskriftsartikel (refereegranskat)abstract
- Being alone or together makes a difference for the photophysics of dyes but for ionic dyes it is difficult to quantify the interactions due to solvent screening and nearby counter ions. Gas-phase luminescence experiments are desirable and now possible based on recent developments in mass spectrometry. Here we present results on tailor-made rhodamine homodimers where two dye cations are separated by methylene linkers, (CH2)(n). In solution the fluorescence is almost identical to that from the monomer whereas the emission from bare cation dimers redshifts with decreasing n. In the absence of screening, the electric field from the charge on one dye is strong enough to polarize the other dye, both in the ground state and in the excited state. An electrostatic model based on symmetric dye responses (equal induced-dipole moments in ground state) captures the underlying physics and demonstrates interaction even at large distances. Our results have possible implications for gas-phase Forster Resonance Energy Transfer.
|
|
| 25. |
- Langeback, A, et al.
(författare)
-
CETSA-based target engagement of taxanes as biomarkers for efficacy and resistance
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 19384-
-
Tidskriftsartikel (refereegranskat)abstract
- The use of taxanes has for decades been crucial for treatment of several cancers. A major limitation of these therapies is inherent or acquired drug resistance. A key to improved outcome of taxane-based therapies is to develop tools to predict and monitor drug efficacy and resistance in the clinical setting allowing for treatment and dose stratification for individual patients. To assess treatment efficacy up to the level of drug target engagement, we have established several formats of tubulin-specific Cellular Thermal Shift Assays (CETSAs). This technique was evaluated in breast and prostate cancer models and in a cohort of breast cancer patients. Here we show that taxanes induce significant CETSA shifts in cell lines as well as in animal models including patient-derived xenograft (PDX) models. Furthermore, isothermal dose response CETSA measurements allowed for drugs to be rapidly ranked according to their reported potency. Using multidrug resistant cancer cell lines and taxane-resistant PDX models we demonstrate that CETSA can identify taxane resistance up to the level of target engagement. An imaging-based CETSA format was also established, which in principle allows for taxane target engagement to be accessed in specific cell types in complex cell mixtures. Using a highly sensitive implementation of CETSA, we measured target engagement in fine needle aspirates from breast cancer patients, revealing a range of different sensitivities. Together, our data support that CETSA is a robust tool for assessing taxane target engagement in preclinical models and clinical material and therefore should be evaluated as a prognostic tool during taxane-based therapies.
|
|
