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- Konradsson, E, et al.
(författare)
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Intracavitary Electron FLASH Radiotherapy in a Canine Cancer Patient With Oral Malignant Melanoma
- 2021
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016. ; 111:3S, s. 31-31
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE/OBJECTIVE(S): Studies of electron FLASH radiotherapy (FLASH-RT) in companion animals are being conducted at several institutions. High energy electron beams are generally suitable for treatment of superficial cancers, but of limited use for deep-seated tumors. In this case report, the feasibility of intracavitary electron FLASH-RT is demonstrated.MATERIALS/METHODS: A canine cancer patient with a large oral malignant melanoma in the caudal part of the hard palate was palliatively treated with FLASH-RT at a modified clinical linear accelerator, using a cylindrical PMMA applicator (length 200 mm, inside diameter 50 mm). The patient had a poor prognosis, with an estimated survival of two weeks and no other available treatment options. A dose of 35 Gy was delivered to the depth of dose maximum in 26 pulses with a pulse dose rate of 4.5•105 Gy/s. The average dose rate was 280 Gy/s, corresponding to a total beam-on time of 125 months. One month after the treatment, the tumor was re-irradiated, using the same treatment parameters. The treatment head of the LINAC was fitted with a short electron applicator holder with a Cerrobend collimator at 65 cm from the source. The cylindrical PMMA applicator was aligned perpendicularly to the Cerrobend collimator using soft docking with a 1 cm gap. Prior to the treatments, the 2D dose distribution of the FLASH beam exiting the PMMA applicator was measured with radiographic film. In addition, the dosimetric effect of misalignment between the collimator and the electron applicator was studied based on intentional misalignments of 2.5°, 5°, 2.5 mm, and 5 mm.RESULTS: A partial response of the tumor and clinical improvement of the patient was observed two weeks after the first treatment. A hypopigmented area in the hard palate was observed, consistent with a grade 1 adverse event, but there were no signs of mucositis or reports of patient discomfort. However, due to the thickness of the tumor (> 3 cm), the posterior part only received a limited dose, and the tumor was still obstructing the airflow at one month post treatment. At this time, a second treatment was administered with limited normal tissue receiving full dose from both treatments. At one month post the second treatment, a partial response was achieved, and no evidence of side effects other than hypopigmentation was observed. The patient was euthanized 2.5 months after the initial therapy due to progressive disease involving the oropharynx. The dosimetric evaluation showed that a conformal dose distribution could be obtained by delivering the electron beam using a cylindrical PMMA applicator. Misalignments between the applicator and the collimator were shown to result in reduced dose homogeneity.CONCLUSION: This case report of a canine cancer patient, with a large oral malignant melanoma in the caudal part of the hard palate, has demonstrated the feasibility of intracavitary electron FLASH-RT. Two treatments of 35 Gy each, resulted in prolonged survival and increased quality-of-life.
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- Titulaer, Joep, et al.
(författare)
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Lumateperone-mediated effects on prefrontal glutamatergic receptor-mediated neurotransmission: A dopamine D-1 receptor dependent mechanism
- 2022
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Ingår i: European Neuropsychopharmacology. - : Elsevier BV. - 0924-977X .- 1873-7862. ; 62, s. 22-35
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Tidskriftsartikel (refereegranskat)abstract
- Lumateperone is a novel drug approved for the treatment of schizophrenia in adults and depressive episodes associated with bipolar depression in adults, as monotherapy and as adjunctive therapy with lithium or valproate treatment in the United States. Lumateperone simultaneously modulates key neurotransmitters, such as serotonin, dopamine, and glutamate, implicated in serious mental illness. In patients with schizophrenia, lumateperone was shown to improve positive symptoms along with negative and depressive symptoms, while also enhancing prosocial behavior. Moreover, in patients with bipolar I or II disorder, lumateperone improved depressive symptoms as well. To further understand the mechanisms related to lumateperone's clinical response, the aim of this study was to investigate the effect of lumateperone on dopaminergic-and glutamatergic signaling in the rat medial prefrontal cortex (mPFC). We used the conditioned avoidance response (CAR) test to determine the antipsychotic-like effect of lumateper one, electrophysiology in vitro to study lumateperone's effects on NMDA-and AMPA-induced currents in the mPFC, and the neurochemical techniques microdialysis and amperometry to measure dopamine-and glutamate release in the rat mPFC. Our results demonstrate that lu-mateperone; i) significantly suppressed CAR in rats, indicating an antipsychotic-like effect, ii) facilitated NMDA and AMPA receptor-mediated currents in the mPFC, in a dopamine D-1-dependent manner, and iii) significantly increased dopamine and glutamate release in the rat mPFC. To the extent that these findings can be translated to humans, the ability of lumate-perone to activate these pathways may contribute to its demonstrated effectiveness in safely improving symptoms related to neuropsychiatric disorder including mood alterations. (C) 2022 The Author(s). Published by Elsevier B.V.
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| 5. |
- Ceberg, S., et al.
(författare)
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FLASH radiotherapy and the associated dosimetric challenges
- 2023
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Ingår i: Journal of Physics: Conference Series. ; 2630
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Konferensbidrag (refereegranskat)abstract
- At Lund University and Skåne University Hospital in Lund, Sweden, we have, as the first clinic, modified a clinical Elekta Precise linear accelerator for convertible delivery of ultrahigh dose rate (FLASH) irradiation. Whereas recently published reviews highlighted the need for standardised protocols for ultra-high dose rate beam dosimetry to be able to determine the true potential of FLASH irradiation, several dosimetry studies as well as in-vitro and in-vivo experiments have been carried out at our unit. Dosimetric procedures for verification of accurate dose delivery of FLASH irradiation to cell cultures, zebrafish embryos and small animals have been established using radiochromic films and thermo-luminescent dosimeters. Also, recently the first experience of electron FLASH radiotherapy (FLASH-RT) in canine patients in our clinical setting was published. Our research facilities also include a laboratory for 3D polymer gel manufacturing. Recently, we started investigating the feasibility of a NIPAM polymer gel dosimeter for ultra-high dose rate dosimetry. Furthermore, in the bunker of the modified Elekta linear accelerator, a Surface Guided Radiotherapy (SGRT) system is accessible. The CatalystTM system (C-Rad Positioning, Uppsala, Sweden) provides optical surface imaging for patient setup, real-time motion monitoring and breathing adapted treatment. Aiming at treating patients using ultra-high dose rates, a real-time validation of the alignment between the beam and the target is crucial as the dose is delivered in a fraction of a second. Our research group has during the last decade investigated and developed SGRT workflows which improved patient setup and breathing adapted treatment for several cancer patient groups. Recently, we also started investigating the feasibility of a real-time motion monitoring system for surface guided FLASH-RT. Both FLASH related studies; 3D polymer gel dosimetry and surface guided FLASH-RT are to our knowledge the first of their kind. Following an introduction to the field of FLASH and the associated dosimetric challenges, we here aim to present the two ongoing studies including some preliminary results.
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- Cortese, Samuele, et al.
(författare)
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Psychopharmacology in children and adolescents: unmet needs and opportunities
- 2024
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Ingår i: The Lancet Psychiatry. - 2215-0366 .- 2215-0374. ; 11:2, s. 143-154
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Forskningsöversikt (refereegranskat)abstract
- Psychopharmacological treatment is an important component of the multimodal intervention approach to treating mental health conditions in children and adolescents. Currently, there are many unmet needs but also opportunities, alongside possible risks to consider, regarding the pharmacological treatment of mental health conditions in children and adolescents. In this Position Paper, we highlight and address these unmet needs and opportunities, including the perspectives of clinicians and researchers from the European College of Neuropsychopharmacology–Child and Adolescent Network, alongside those of experts by lived experience from national and international associations, via a survey involving 644 participants from 13 countries, and of regulators, through representation from the European Medicines Agency. We present and discuss the evidence base for medications currently used for mental disorders in children and adolescents, medications in the pipeline, opportunities in the development of novel medications, crucial priorities for the conduct of future clinical studies, challenges and opportunities in terms of the regulatory and legislative framework, and innovations in the way research is conducted, reported, and promoted.
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| 9. |
- Garegg, P.J., et al.
(författare)
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Transglucosidation of methyl and ethyl D-glucopyranosides by alcoholysis
- 2002
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Ingår i: Carbohydrate Research. - 0008-6215 .- 1873-426X. ; 337:6, s. 517-521
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Tidskriftsartikel (refereegranskat)abstract
- The transglucosidations of methyl 4-O-methyl-a- and -ß-D-glucopyranoside in ethanolic camphor-10-sulfonic acid, and of ethyl 4-O-methyl-a- and -ß-D-glucopyranoside in methanolic camphor-10-sulfonic acid, have been studied. Samples were removed at intervals and the proportions of the glucosides determined by GC of their acetates. The results show that the anomer with the inverted configuration predominates in the initially formed product (˜59-70%). This indicates that all the studied reactions proceed via the same mechanism, involving exocyclic C-O cleavage and formation of a glucopyranosylium ion, but that the eliminated alcohol exerts some steric hindrance, which favors the approach of the other alcohol from the opposite side. © 2002 Published by Elsevier Science Ltd.
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