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- Frantz, A M, et al.
(author)
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Molecular Profiling Reveals Prognostically Significant Subtypes of Canine Lymphoma
- 2013
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In: Veterinary pathology. - : SAGE Publications. - 0300-9858 .- 1544-2217. ; 50:4, s. 693-703
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Journal article (peer-reviewed)abstract
- We performed genomewide gene expression analysis of 35 samples representing 6 common histologic subtypes of canine lymphoma and bioinformatics analyses to define their molecular characteristics. Three major groups were defined on the basis of gene expression profiles: (1) low-grade T-cell lymphoma, composed entirely by T-zone lymphoma; (2) high-grade T-cell lymphoma, consisting of lymphoblastic T-cell lymphoma and peripheral T-cell lymphoma not otherwise specified; and (3) B-cell lymphoma, consisting of marginal B-cell lymphoma, diffuse large B-cell lymphoma, and Burkitt lymphoma. Interspecies comparative analyses of gene expression profiles also showed that marginal B-cell lymphoma and diffuse large B-cell lymphoma in dogs and humans might represent a continuum of disease with similar drivers. The classification of these diverse tumors into 3 subgroups was prognostically significant, as the groups were directly correlated with event-free survival. Finally, we developed a benchtop diagnostic test based on expression of 4 genes that can robustly classify canine lymphomas into one of these 3 subgroups, enabling a direct clinical application for our results.
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| 3. |
- Borgatti, Antonella, et al.
(author)
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Safe and Effective Sarcoma Therapy through Bispecific Targeting of EGFR and uPAR.
- 2017
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In: Molecular Cancer Therapeutics. - 1535-7163 .- 1538-8514. ; 16:5, s. 956-965
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Journal article (peer-reviewed)abstract
- Sarcomas differ from carcinomas in their mesenchymal origin. Therapeutic advancements have come slowly so alternative drugs and models are urgently needed. These studies report a new drug for sarcomas that simultaneously targets both tumor and tumor neovasculature. eBAT is a bispecific angiotoxin consisting of truncated, deimmunized Pseudomonas exotoxin fused to epidermal growth factor (EGF) and the amino terminal fragment (ATF) of urokinase. Here, we study the drug in an in vivo "ontarget" companion dog trial since eBAT effectively kills canine hemangiosarcoma (HSA) and human sarcoma cells in vitro. We reasoned the model has value due to the common occurrence of spontaneous sarcomas in dogs and a limited lifespan allowing for rapid accrual and data collection. Splenectomized dogs with minimal residual disease were given one cycle of eBAT followed by adjuvant doxorubicin in an adaptive dose-finding, phase I-II study of 23 dogs with spontaneous, stage I-II, splenic HSA. eBAT improved 6-month survival from <40% in a comparison population to ~70% in dogs treated at a biologically active dose (50 µg/kg). Six dogs were long-term survivors, living >450 days. eBAT abated expected toxicity associated with EGFR-targeting, a finding supported by mouse studies. Urokinase plasminogen activator receptor (uPAR) and EGFR are targets for human sarcomas, so thorough evaluation is crucial for validation of the dog model. Thus, we validated these markers for human sarcoma targeting in the study of 212 human and 97 canine sarcoma samples. Our results support further translation of eBAT for human patients with sarcomas and perhaps other EGFR-expressing malignancies.
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| 4. |
- Dediu, V., et al.
(author)
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Room-temperature spintronic effects in Alq3 -based hybrid devices
- 2008
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In: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 78:11
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Journal article (peer-reviewed)abstract
- We report on efficient spin polarized injection and transport in long (102 nm) channels of Alq3 organic semiconductor. We employ vertical spin valve devices with a direct interface between the bottom manganite electrode and Alq3, while the top-electrode geometry consists of an insulating tunnel barrier placed between the "soft" organic semiconductor and the top Co electrode. This solution reduces the ubiquitous problem of the so-called ill-defined layer caused by metal penetration, which extends into the organic layer up to distances of about 50-100 nm and prevents the realization of devices with well-defined geometry. For our devices the thickness is defined with an accuracy of about 2.5 nm, which is near the Alq3 molecular size. We demonstrate efficient spin injection at both interfaces in devices with 100- and 200-nm-thick channels. We solve one of the most controversial problems of organic spintronics: the temperature limitations for spin transport in Alq3 -based devices. We clarify this issue by achieving room-temperature spin valve operation through the improvement of spin injection properties of both ferromagnetic/ Alq3 interfaces. In addition, we discuss the nature of the inverse sign of the spin valve effect in such devices proposing a mechanism for spin transport. © 2008 The American Physical Society.
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- Graziosi, Patrizio, et al.
(author)
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Conditions for the growth of smooth La 0.7 Sr 0.3 MnO 3 thin films by pulsed electron ablation
- 2013
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In: Thin Solid Films. - : Elsevier BV. - 0040-6090. ; 534, s. 83-89
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Journal article (peer-reviewed)abstract
- We report on the optimisation of the growth conditions of manganite La 0.7 Sr 0.3 MnO 3 thin films prepared by Channel Spark Ablation (CSA). CSA belongs to pulsed electron deposition methods and its energetic and deposition parameters are quite similar to those of pulsed laser deposition. The method has been already proven to provide manganite films with good magnetic properties, but the films were generally relatively rough (a few nm coarseness). Here we show that increasing the oxygen deposition pressure with respect to previously used regimes, reduces the surface roughness down to unit cell size while maintaining a robust magnetism. We analyse in detail the effect of other deposition parameters, like accelerating voltage, discharging energy, chamber pressure and substrate temperature and provide on this basis a set of optimal conditions for the growth of atomically flat films. The thicknesses for which atomically flat surface was achieved is as high as about 10-20 nm, corresponding to films with room temperature magnetism. We believe such magnetic layers represent appealing and suitable electrodes for various spintronic devices. © 2013 Elsevier B.V.
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| 6. |
- Oliver, D, et al.
(author)
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Prognostic accuracy and clinical utility of psychometric instruments for individuals at clinical high-risk of psychosis: a systematic review and meta-analysis
- 2022
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In: Molecular psychiatry. - : Springer Science and Business Media LLC. - 1476-5578 .- 1359-4184. ; 27:9, s. 3670-3678
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Research review (other academic/artistic)abstract
- Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P−). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan’s nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12–40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81–0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87–0.96) and poor specificity (0.58, 95% CI: 0.50–0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81–2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06−0.21) for developing psychosis. Fagan’s nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1–25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.
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