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  1. Article ; Online: Unraveling the cartography of the cancer ecosystem

    Roy Rabbie / Doreen Lau / Richard M. White / David J. Adams

    Genome Biology, Vol 22, Iss 1, Pp 1-

    2021  Volume 9

    Keywords Biology (General) ; QH301-705.5 ; Genetics ; QH426-470
    Language English
    Publishing date 2021-03-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Interferon-γ couples CD8+ T cell avidity and differentiation during infection

    Lion F. K. Uhl / Han Cai / Sophia L. Oram / Jagdish N. Mahale / Andrew J. MacLean / Julie M. Mazet / Theo Piccirilli / Alexander J. He / Doreen Lau / Tim Elliott / Audrey Gerard

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 17

    Abstract: Abstract Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth ...

    Abstract Abstract Effective responses to intracellular pathogens are characterized by T cell clones with a broad affinity range for their cognate peptide and diverse functional phenotypes. How T cell clones are selected throughout the response to retain a breadth of avidities remains unclear. Here, we demonstrate that direct sensing of the cytokine IFN-γ by CD8+ T cells coordinates avidity and differentiation during infection. IFN-γ promotes the expansion of low-avidity T cells, allowing them to overcome the selective advantage of high-avidity T cells, whilst reinforcing high-avidity T cell entry into the memory pool, thus reducing the average avidity of the primary response and increasing that of the memory response. IFN-γ in this context is mainly provided by virtual memory T cells, an antigen-inexperienced subset with memory features. Overall, we propose that IFN-γ and virtual memory T cells fulfil a critical immunoregulatory role by enabling the coordination of T cell avidity and fate.
    Keywords Science ; Q
    Subject code 612
    Language English
    Publishing date 2023-10-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Feed Restriction Modulates Growth, Gut Morphology and Gene Expression in Zebrafish

    Kathiresan Purushothaman / Jerryl Kim Han Tan / Doreen Lau / Jolly M. Saju / Natascha M. Thevasagayam / Caroline Lei Wee / Shubha Vij

    International Journal of Molecular Sciences, Vol 22, Iss 4, p

    2021  Volume 1814

    Abstract: A reduction in daily caloric or nutrient intake has been observed to promote health benefits in mammals and other vertebrates. Feed Restriction (FR), whereby the overall food intake of the organism is reduced, has been explored as a method to improve ... ...

    Abstract A reduction in daily caloric or nutrient intake has been observed to promote health benefits in mammals and other vertebrates. Feed Restriction (FR), whereby the overall food intake of the organism is reduced, has been explored as a method to improve metabolic and immune health, as well as to optimize productivity in farming. However, less is known regarding the molecular and physiological consequences of FR. Using the model organism, Danio rerio , we investigated the impact of a short-term (month-long) FR on growth, gut morphology and gene expression. Our data suggest that FR has minimal effects on the average growth rates, but it may affect weight and size heterogeneity in a sex-dependent manner. In the gut, we observed a significant reduction in gut circumference and generally lower mucosal heights, whereas other parameters remained unchanged. Gene Ontology (GO), EuKaryotic Orthologous Groups (KOG), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis identified numerous metabolic, reproductive, and immune response pathways that were affected by FR. These results broaden our understanding of FR and contribute towards growing knowledge of its effects on vertebrate health.
    Keywords Danio rerio ; gut ; calorie restriction ; feed restriction ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Radiofluorination of a highly potent ATM inhibitor as a potential PET imaging agent

    Claudia Rose Fraser / Javier Ajenjo / Mathew Veal / Gemma Marie Dias / Chung Chan / Edward O’Neill / Gianluca Destro / Doreen Lau / Anna Pacelli / Veronique Gouverneur / Rebekka Hueting / Bart Cornelissen

    EJNMMI Research, Vol 12, Iss 1, Pp 1-

    2022  Volume 12

    Abstract: Abstract Purpose Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug ... ...

    Abstract Abstract Purpose Ataxia telangiectasia mutated (ATM) is a key mediator of the DNA damage response, and several ATM inhibitors (ATMi) are currently undergoing early phase clinical trials for the treatment of cancer. A radiolabelled ATMi to determine drug pharmacokinetics could assist patient selection in a move towards more personalised medicine. The aim of this study was to synthesise and investigate the first 18F-labelled ATM inhibitor [18F]1 for non-invasive imaging of ATM protein and ATMi pharmacokinetics. Methods Radiofluorination of a confirmed selective ATM inhibitor (1) was achieved through substitution of a nitro-precursor with [18F]fluoride. Uptake of [18F]1 was assessed in vitro in H1299 lung cancer cells stably transfected with shRNA to reduce expression of ATM. Blocking studies using several non-radioactive ATM inhibitors assessed binding specificity to ATM. In vivo biodistribution studies were performed in wild-type and ATM-knockout C57BL/6 mice using PET/CT and ex vivo analysis. Uptake of [18F]1 in H1299 tumour xenografts was assessed in BALB/c nu/nu mice. Results Nitro-precursor 2 was synthesised with an overall yield of 12%. Radiofluorination of 2 achieved radiochemically pure [18F]1 in 80 ± 13 min with a radiochemical yield of 20 ± 13% (decay-corrected) and molar activities up to 79.5 GBq/μmol (n = 11). In vitro, cell-associated activity of [18F]1 increased over 1 h, and retention of [18F]1 dropped to 50% over 2 h. [18F]1 uptake did not correlate with ATM expression, but could be reduced significantly with an excess of known ATM inhibitors, demonstrating specific binding of [18F]1 to ATM. In vivo, fast hepatobiliary clearance was observed with tumour uptake ranging 0.13–0.90%ID/g after 1 h. Conclusion Here, we report the first radiofluorination of an ATM inhibitor and its in vitro and in vivo biological evaluations, revealing the benefits but also some limitations of 18F-labelled ATM inhibitors.
    Keywords PET ; ATM ; Cancer ; Molecular imaging ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Detection limit of 89Zr-labeled T cells for cellular tracking

    Laura M. Lechermann / Roido Manavaki / Bala Attili / Doreen Lau / Lorna B. Jarvis / Tim D. Fryer / Nick Bird / Luigi Aloj / Neel Patel / Bristi Basu / Matthew Cleveland / Franklin I. Aigbirhio / Joanne L. Jones / Ferdia A. Gallagher

    EJNMMI Research, Vol 10, Iss 1, Pp 1-

    an in vitro imaging approach using clinical PET/CT and PET/MRI

    2020  Volume 12

    Abstract: Abstract Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t 1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 ...

    Abstract Abstract Purpose Tracking cells in vivo using imaging can provide non-invasive information to understand the pharmacology, efficacy, and safety of novel cell therapies. Zirconium-89 (t 1/2 = 78.4 h) has recently been used to synthesize [89Zr]Zr(oxinate)4 for cell tracking using positron emission tomography (PET). This work presents an in vitro approach to estimate the detection limit for in vivo PET imaging of Jurkat T cells directly labeled with [89Zr]Zr(oxinate)4 utilizing clinical PET/CT and PET/MRI. Methods Jurkat T cells were labeled with varying concentrations of [89Zr]Zr(oxinate)4 to generate different cell-specific activities (0.43–31.91 kBq/106 cells). Different concentrations of labeled cell suspensions (104, 105, and 106 cells) were seeded on 6-well plates and into a 3 × 3 cubic-well plate with 1 cm3 cubic wells as a gel matrix. Plates were imaged on clinical PET/CT and PET/MRI scanners for 30 min. The total activity in each well was determined by drawing volumes of interest over each well on PET images. The total cell-associated activity was measured using a well counter and correlated with imaging data. Simulations for non-specific signal were performed to model the effect of non-specific radioactivity on detection. Results Using this in vitro model, the lowest cell number that could be visualized on 6-well plate images was 6.8 × 104, when the specific activity was 27.8 kBq/106 cells. For the 3 × 3 cubic-well, a plate of 3.3 × 104 cells could be detected on images with a specific activity of 15.4 kBq/106 cells. Conclusion The results show the feasibility of detecting [89Zr]Zr(oxinate)4-labeled Jurkat T cells on clinical PET systems. The results provide a best-case scenario, as in vivo detection using PET/CT or PET/MRI will be affected by cell number, specific activity per cell, the density of cells within the target volume, and non-specific signal. This work has important implications for cell labeling studies in patients, particularly when using radiosensitive cells (e.g., T cells), which require ...
    Keywords PET ; Cell labeling ; Cell tracking ; Zirconium-89 ; Detection limit ; Medical physics. Medical radiology. Nuclear medicine ; R895-920
    Subject code 610
    Language English
    Publishing date 2020-07-01T00:00:00Z
    Publisher SpringerOpen
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Morpho-histological characterisation of the alimentary canal of an important food fish, Asian seabass (Lates calcarifer)

    Kathiresan Purushothaman / Doreen Lau / Jolly M. Saju / Syed Musthaq SK / Declan Patrick Lunny / Shubha Vij / László Orbán

    PeerJ, Vol 4, p e

    2016  Volume 2377

    Abstract: Asian seabass (Lates calcarifer) is a food fish of increasing aquaculture importance. In order to improve our understanding on the digestive system and feeding of this species, morphological and histological features of the gut were studied. ... ...

    Abstract Asian seabass (Lates calcarifer) is a food fish of increasing aquaculture importance. In order to improve our understanding on the digestive system and feeding of this species, morphological and histological features of the gut were studied. Morphologically, the Asian seabass gut is defined by a short and muscular esophagus, well-developed stomach and comparatively short intestine. Mucous secreting goblet cells reactive to PAS (Periodic Acid Schiff) and AB (Alcian Blue) stain were present throughout the esophagus. The stomach was sac-like and could be distinguished into the cardiac, fundic and pyloric regions. Gastric glands and mucus cells were predominately present in the cardiac and fundic regions. Five finger-like pyloric caeca were present between the stomach and intestine. The intestine was a short, tubular structure with no morphological differences between the various regions. Histologically, the intestinal regions were similar, the main difference being in the number of goblet cells that increased from anterior to posterior intestine, with 114 ± 9, 153 ± 7 and 317 ± 21 goblet cells in the anterior, mid and posterior regions, respectively. The intestinal epithelium stained positively for PAS, but the staining was stronger for acidic glycoproteins. The rectum was similar to intestine, except for increased goblet cell numbers (anterior rectum: 529 ± 26; posterior rectum: 745 ± 29). Gut morpho-histology did not respond to salinity changes, however, there was a significant reduction of mucosal height, goblet cell numbers and muscularis thickness upon food deprivation.
    Keywords Gut ; Lates calcarifer ; Morphohistology ; Fish alimentary canal ; Medicine ; R ; Biology (General) ; QH301-705.5
    Subject code 590
    Language English
    Publishing date 2016-08-01T00:00:00Z
    Publisher PeerJ Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

    Roy Rabbie / Naser Ansari-Pour / Oliver Cast / Doreen Lau / Francis Scott / Sarah J. Welsh / Christine Parkinson / Leila Khoja / Luiza Moore / Mark Tullett / Kim Wong / Ingrid Ferreira / Julia M. Martínez Gómez / Mitchell Levesque / Ferdia A. Gallagher / Alejandro Jiménez-Sánchez / Laura Riva / Martin L. Miller / Kieren Allinson /
    Peter J. Campbell / Pippa Corrie / David C. Wedge / David J. Adams

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of ... ...

    Abstract Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
    Keywords Science ; Q
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: Multi-site clonality analysis uncovers pervasive heterogeneity across melanoma metastases

    Roy Rabbie / Naser Ansari-Pour / Oliver Cast / Doreen Lau / Francis Scott / Sarah J. Welsh / Christine Parkinson / Leila Khoja / Luiza Moore / Mark Tullett / Kim Wong / Ingrid Ferreira / Julia M. Martínez Gómez / Mitchell Levesque / Ferdia A. Gallagher / Alejandro Jiménez-Sánchez / Laura Riva / Martin L. Miller / Kieren Allinson /
    Peter J. Campbell / Pippa Corrie / David C. Wedge / David J. Adams

    Nature Communications, Vol 11, Iss 1, Pp 1-

    2020  Volume 12

    Abstract: Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of ... ...

    Abstract Metastatic melanoma is associated with a poor prognosis and understanding the genetic features of metastases may enable better treatment strategies. Here, the authors analyse multiple metastases from individual patients finding high levels of heterogeneity in metastases from different organs.
    Keywords Science ; Q
    Language English
    Publishing date 2020-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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