| 1. |
- Jentschel, M., et al.
(författare)
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EXILL - a high-efficiency, high-resolution setup for gamma-spectroscopy at an intense cold neutron beam facility
- 2017
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- In the EXILL campaign a highly efficient array of high purity germanium (HPGe) detectors was operated at the cold neutron beam facility PF1B of the Institut Laue-Langevin (ILL) to carry out nuclear structure studies, via measurements of gamma-rays following neutron-induced capture and fission reactions. The setup consisted of a collimation system producing a pencil beam with a thermal capture equivalent flux of about 10(8) ns(-1)cm(2) at the target position and negligible neutron halo. The targetwas surrounded by an array of eight to ten anti-Compton shielded EXOGAMClover detectors, four to six anti-Compton shielded large coaxial GASP detectors and two standard Clover detectors. For a part of the campaign the array was combined with 16 LaBr3:(Ce) detectors from the FATIMA collaboration. The detectorswere arranged in an array of rhombicuboctahedron geometry, providing the possibility to carry out very precise angular correlation and directional-polarization correlation measurements. The triggerless acquisition system allowed a signal collection rate of up to 6 x 10(5) Hz. The data allowed to set multi-fold coincidences to obtain decay schemes and in combination with the FATIMA array of LaBr3:(Ce) detectors to analyze half-lives of excited levels in the pico-to microsecond range. Precise energy and efficiency calibrations of EXILL were performed using standard calibration sources of Ba-133, Co-60 and Eu-152 as well as data from the reactions Al-27(n, gamma)Al-28 and Cl-35(n,gamma)Cl-36 in the energy range from 30 keV up to 10MeV.
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| 2. |
- Michaut, Magali, et al.
(författare)
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Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.
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| 3. |
- Brennan, D. J., et al.
(författare)
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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
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Ingår i: Oncogene. - : Springer Science and Business Media LLC. - 1476-5594 .- 0950-9232. ; 31:30, s. 3483-3494
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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
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| 4. |
- Severson, Tesa M, et al.
(författare)
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BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.
- 2015
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 9:8, s. 1528-1538
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Tidskriftsartikel (refereegranskat)abstract
- Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors.
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| 5. |
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| 6. |
- Gouzi, Jean Y., et al.
(författare)
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The receptor tyrosine kinase alk controls neurofibromin functions in drosophila growth and learning
- 2011
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Ingår i: PLoS Genetics. - San Francisco Calif. : Public Library of Science. - 1553-7390 .- 1553-7404. ; 7:9, s. e1002281-
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Tidskriftsartikel (refereegranskat)abstract
- Anaplastic Lymphoma Kinase (Alk) is a Receptor Tyrosine Kinase (RTK) activated in several cancers, but with largely unknown physiological functions. We report two unexpected roles for the Drosophila ortholog dAlk, in body size determination and associative learning. Remarkably, reducing neuronal dAlk activity increased body size and enhanced associative learning, suggesting that its activation is inhibitory in both processes. Consistently, dAlk activation reduced body size and caused learning deficits resembling phenotypes of null mutations in dNf1, the Ras GTPase Activating Protein-encoding conserved ortholog of the Neurofibromatosis type 1 (NF1) disease gene. We show that dAlk and dNf1 co-localize extensively and interact functionally in the nervous system. Importantly, genetic or pharmacological inhibition of dAlk rescued the reduced body size, adult learning deficits, and Extracellular-Regulated-Kinase (ERK) overactivation dNf1 mutant phenotypes. These results identify dAlk as an upstream activator of dNf1-regulated Ras signaling responsible for several dNf1 defects, and they implicate human Alk as a potential therapeutic target in NF1.
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| 7. |
- Gürdal, G., et al.
(författare)
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Measurements of g(41+,22+) in 70,72,74 ,76Ge: Systematics of low-lying structures in 30≤Z≤40 and 30≤N≤50 nuclei
- 2013
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Ingår i: Physical Review C - Nuclear Physics. - 2469-9985 .- 2469-9993. ; 88:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The interplay between single-particle and collective excitations in the 30 ≤Z≤ 40 and 30 ≤N≤ 50 even-even isotopes has been examined in light of recent new measurements of magnetic moments of 41+, 22+, and 21+ states. Purpose: The g factors of the 41+ and 22+ states in the 72,74,76Ge isotopes have been measured for the first time and the g(21+) values have been remeasured. Methods: The transient field (TF) technique in inverse kinematics with a variety of targets has been applied, following Coulomb excitation of the relevant states. The data have been analyzed within the framework of the IBA-II model. Large-scale shell-model calculations have been performed within the p3/2,p1/2,f 5/2,g9/2 orbital space for both protons and neutrons with the JUN45 and JJ4B interactions. Results: The measured Ge g factors were compared to the g factors of the low-lying states of the neighboring Zn, Ge, Se, Kr, and Sr isotopes. The results were evaluated in the context of the systematics of g factors in the A∼80 region. Conclusions: The predictions based on the classic collective model and the interacting boson model IBA-II agree with the experimental results. No evidence for shell closure was found for neutrons at N=38 or N=40. © 2013 American Physical Society.
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