SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Crona Joakim) ;pers:(Beuschlein Felix)"

Sökning: WFRF:(Crona Joakim) > Beuschlein Felix

  • Resultat 1-7 av 7
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Crona, Joakim, et al. (författare)
  • Adrenocortical carcinoma : towards genomics guided clinical care
  • 2019
  • Ingår i: Nature Reviews Endocrinology. - : Springer Science and Business Media LLC. - 1759-5029 .- 1759-5037. ; 15:9, s. 548-560
  • Forskningsöversikt (refereegranskat)abstract
    • Adrenocortical carcinoma (ACC) is an aggressive and rare neoplasm that originates in the cortex of the adrenal gland. The disease is associated with heterogeneous but mostly poor outcomes and lacks effective pharmaceutical treatment options. Multi-omics studies have defined the landscape of molecular alterations in ACC. Specific molecular signatures can be detected in body fluids, potentially enabling improved diagnostic applications for patients with adrenal tumours. Importantly, pan-molecular data sets further reveal a spectrum within ACC, with three major subgroups that have different disease outcomes. These new subgroups have value as prognostic biomarkers. Research has revealed that the p53-RB and the WNT-beta-catenin pathways are common disease drivers in ACC. However, these pathways remain difficult to target by therapeutic interventions. Instead, a unique characteristic of ACC is steroidogenic differentiation, which has emerged as a potential treatment target, with several agents undergoing preclinical or clinical investigations. Finally, a large proportion of ACC tumours have genetic profiles that are associated with promising therapeutic responsiveness in other cancers. All these opportunities now await translation from the laboratory into the clinical setting, thereby offering a real potential of improved survival outcomes and increased quality of life for patients with this serious condition.
  •  
2.
  • Crona, Joakim (författare)
  • Charting the Genetic Landscape and Clonal Architectures of Pheochromocytoma
  • 2014
  • Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
    • Genotypic and phenotypic inter patient heterogeneity characterize pheochromocytoma and paraganglioma (PPGL). Up to 60% of PPGL are associated with either somatic or germline mutations in at least 14 established disease causing genes. Consequently, a comprehensive screening test for PPGL patients utilizing standard techniques is not feasible and in the diagnostic approach, multiple different phenotype guided gene prioritization protocols have been utilized. This may result in misdiagnosis, especially in patients with sporadic presentation. Diagnostic testing of somatic mutations in tumour material is not performed due to the lack of actionable results.The aims of this study were, (1) to investigate the use of novel sequencing techniques in a clinical application, (2) to discover novel PPGL disease causing loci using novel sequencing techniques, (3) to characterize a large cohort of PPGL for mutations in known disease causing genes and to analyse corresponding genotype-phenotype correlations, (4) to dissect the molecular and genetic landscape of MEN2 PPGL and (5) to determine the clonal architecture and heterogeneity within, and in-between matched PPGL.For these purposes we studied PPGL tumours from a total of 96 patients using targeted and/or whole exome enrichment, capillary and high throughput sequencing as well as genome wide array based genotyping. Novel bioinformatics pipelines were constructed for raw data processing and downstream interpretation. Quantitative PCR, western blot and immunohistochemistry were utilized in order to characterize molecular traits. Selected experimental findings were correlated to patient phenotype.We conclude that novel sequencing techniques could be utilized in clinical genetic screening of patients with PPGL. Somatic gain-of-function mutations in H-RAS are likely to contribute to disease pathogenesis. Analysing tumour DNA for somatic mutations in disease causing genes could provide relevant clinical information and have an impact on patient management. Concomitant mutations in PPGL may occur in exceptional cases and have a substantial impact on tumour biology and patient phenotype. And finally genetic heterogeneity is present between and within a majority of PPGL tumours.
  •  
3.
  • Crona, Joakim, et al. (författare)
  • ENSAT registry-based randomized clinical trials for adrenocortical carcinoma
  • 2021
  • Ingår i: European Journal of Endocrinology. - : Bioscientifica. - 0804-4643 .- 1479-683X. ; 184:2, s. R51-R59
  • Forskningsöversikt (refereegranskat)abstract
    • Adrenocortical carcinoma (ACC) is an orphan disease lacking effective systemic treatment options. The low incidence of the disease and high cost of clinical trials are major obstacles in the search for improved treatment strategies. As a novel approach, registry-based clinical trials have been introduced in clinical research, so allowing for significant cost reduction, but without compromising scientific benefit. Herein, we describe how the European Network for the Study of Adrenal Tumours (ENSAT) could transform its current registry into one fit for a clinical trial infrastructure. The rationale to perform randomized registry-based trials in ACC is outlined including an analysis of relevant limitations and challenges. We summarize a survey on this concept among ENSAT members who expressed a strong interest in the concept and rated its scientific potential as high. Legal aspects, including ethical approval of registry-based randomization were identified as potential obstacles. Finally, we describe three potential randomized registry-based clinical trials in an adjuvant setting and for advanced disease with a high potential to be executed within the framework of an advanced ENSAT registry. Thus we, therefore, provide the basis for future registry-based trials for ACC patients. This could ultimately provide proof-of-principle of how to perform more effective randomized trials for an orphan disease.
  •  
4.
  • Jiang, Jingjing, et al. (författare)
  • Sino-European Differences in the Genetic Landscape and Clinical Presentation of Pheochromocytoma and Paraganglioma
  • 2020
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 105:10
  • Tidskriftsartikel (refereegranskat)abstract
    • Context: Pheochromocytomas and paragangliomas (PPGLs) are characterized by distinct genotype-phenotype relationships according to studies largely restricted to Caucasian populations.Objective: To assess for possible differences in genetic landscapes and genotype-phenotype relationships of PPGLs in Chinese versus European populations.Design: Cross-sectional study.Setting: 2 tertiary-care centers in China and 9 in Europe.Participants: Patients with pathologically confirmed diagnosis of PPGL, including 719 Chinese and 919 Europeans.Main Outcome Measures: Next-generation sequencing performed in tumor specimens with mutations confirmed by Sanger sequencing and tested in peripheral blood if available. Frequencies of mutations were examined according to tumor location and catecholamine biochemical phenotypes.Results: Among all patients, higher frequencies of HRAS, FGFR1, and EPAS1 mutations were observed in Chinese than Europeans, whereas the reverse was observed for NF1, VHL, RET, and SDHx. Among patients with apparently sporadic PPGLs, the most frequently mutated genes in Chinese were HRAS (16.5% [13.6-19.3] vs 9.8% [7.6-12.1]) and FGFR1 (9.8% [7.6-12.11 vs 2.2% [1.1-3.3]), whereas among Europeans the most frequently mutated genes were NF1 (15.9% [13.2-18.6) vs 6.6% [4.7-8.5)) and SDHx (10.7% [8.4-13.0] vs 4.2% [2.6-5.7]). Among Europeans, almost all paragangliomas lacked appreciable production of epinephrine and identified gene mutations were largely restricted to those leading to stabilization of hypoxia inducible factors. In contrast, among Chinese there was a larger proportion of epinephrine-producing paragangliomas, mostly due to HRAS and FGFR1 mutations.Conclusions: This study establishes Sino-European differences in the genetic landscape and presentation of PPGLs, including ethnic differences in genotype-phenotype relationships indicating a paradigm shift in our understanding of the biology of these tumors.
  •  
5.
  • Wang, Katharina, et al. (författare)
  • Targeted Therapies in Pheochromocytoma and Paraganglioma
  • 2022
  • Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 107:11, s. 2963-2972
  • Forskningsöversikt (refereegranskat)abstract
    • Molecular targeted therapy plays an increasingly important role in the treatment of metastatic pheochromocytomas and paragangliomas (PPGLs), which are rare tumors but remain difficult to treat. This mini-review provides an overview of established molecular targeted therapies in present use, and perspectives on those currently under development and evaluation in clinical trials. Recently published research articles, guidelines, and expert views on molecular targeted therapies in PPGLs are systematically reviewed and summarized. Some tyrosine kinase inhibitors (sunitinib, cabozantinib) are already in clinical use with some promising results, but without formal approval for the treatment of PPGLs. Sunitinib is the only therapeutic option which has been investigated in a randomized placebo-controlled clinical trial. It is clinically used as a first-, second-, or third-line therapeutic option for the treatment of progressive metastatic PPGLs. Some other promising molecular targeted therapies (hypoxia-inducible factor 2 alpha [HIF2 alpha] inhibitors, tumor vaccination together with checkpoint inhibitors, antiangiogenic therapies, kinase signaling inhibitors) are under evaluation in clinical trials. The HIF2 alpha inhibitor belzutifan may prove to be particularly interesting for cluster 1B-/VHL/EPAS1-related PPGLs, whereas antiangiogenic therapies seem to be primarily effective in cluster 1A-/SDHx-related PPGLs. Some combination therapies currently being evaluated in clinical trials, such as temozolomide/olaparib, temozolomide/talazoparib, or cabozantinib/atezolizumab, will provide data for novel therapy for metastatic PPGLs. It is likely that advances in such molecular targeted therapies will play an essential role in the future treatment of these tumors, with more personalized therapy options paving the way towards improved therapeutic outcomes.
  •  
6.
  •  
7.
  • Zhang, Liang, et al. (författare)
  • Risk of complications after core needle biopsy in pheochromocytoma/paraganglioma
  • 2023
  • Ingår i: Endocrine-Related Cancer. - : Bioscientifica. - 1351-0088 .- 1479-6821. ; 30:7
  • Tidskriftsartikel (refereegranskat)abstract
    • Core needle biopsy (CNB) has been used with caution in pheochromocytoma and paraganglioma (PPGL) due to concerns about catecholamine-related complications. While it is unclear what scientific evidence supports this claim, it has limited the acquisition of biological samples for diagnostic purposes and research, especially in metastatic PPGL. We performed a systematic review and individual patient meta-analysis to evaluate the risk of complications after CNB in PPGL patients. The primary and secondary objectives were to investigate the risk of death and the occurrence of complications requiring intervention or hospitalization, respectively. Fifty-six articles describing 86 PPGL patients undergoing CNB were included. Of the patients (24/71), 34% had metastases and 53.4% (31/58) had catecholamine-related symptoms before CNB. Of the patients (14/41), 34.1% had catecholamine excess testing prior to the biopsy. No CNB-related deaths were reported. Four patients (14.8%, 4/27) experienced CNB-related complications requiring hospitalization or intervention. One case had a temporary duodenal obstruction caused by hematoma, two cases had myocardial infarction, and one case had Takotsubo cardiomyopathy. Eight patients (32%, 8/25) had CNB-related catecholamine symptoms, mainly transient hypertension, excessive diaphoresis, tachycardia, or hypertensive crisis. The scientific literature does not allow us to make any firm conclusion on the safety of CNB in PPGL. However, it is reasonable to argue that CNB could be conducted after thorough consideration, preparation, and with close follow-up for PPGL patients with a strong clinical indication for such investigation.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-7 av 7
Typ av publikation
tidskriftsartikel (3)
forskningsöversikt (3)
doktorsavhandling (1)
Typ av innehåll
refereegranskat (5)
övrigt vetenskapligt/konstnärligt (2)
Författare/redaktör
Crona, Joakim (7)
Åkerström, Tobias (3)
Zhang, Liang (3)
Pacak, Karel (3)
Skogseid, Britt (2)
visa fler...
Mollazadegan, Kazhan (2)
Fassnacht, Martin (2)
Quinkler, Marcus (2)
Gao, Xin (1)
Grossman, Ashley B. (1)
Baudin, Eric (1)
Berruti, Alfredo (1)
Robledo, Mercedes (1)
Arnaldi, Giorgio (1)
Gimenez-Roqueplo, An ... (1)
Terzolo, Massimo (1)
Bancos, Irina (1)
Borson-Chazot, Franc ... (1)
Angelousi, Anna (1)
Zhang, Jing (1)
Guo, Wei (1)
Björklund, Peyman, P ... (1)
Beuschlein, Felix, P ... (1)
Chrisoulidou, Alexan ... (1)
Ronchi, Cristina L. (1)
Oliveira, Cristina L ... (1)
van Dijkum, Els J. M ... (1)
Ceccato, Filippo (1)
Reimondo, Giuseppe (1)
Tiberi, Guido A. M. (1)
Ettaieb, Hester (1)
Kiriakopoulos, Andre ... (1)
Letizia, Canu (1)
Kastelan, Darko (1)
Osher, Esthr (1)
Yiannakopoulou, Euge ... (1)
Assie, Guillaume (1)
Paiva, Isabel (1)
Bourdeau, Isabelle (1)
Newell-Price, John (1)
Nowak, Karolina M. (1)
Romero, M. Tous (1)
De Martino, Maria Cr ... (1)
Bugalho, Maria Joao (1)
Sherlock, Mark (1)
Vantyghem, Marie-Chr ... (1)
Dennedy, Michael Con ... (1)
Loli, Paula (1)
Rodien, Patrice (1)
visa färre...
Lärosäte
Uppsala universitet (7)
Språk
Engelska (7)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (7)

År

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy