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  1. Article: Methionine cycle-dependent regulation of T cells in cancer immunity.

    Zhao, Tian / Lum, Julian J

    Frontiers in oncology

    2022  Volume 12, Page(s) 969563

    Abstract: The methionine cycle comprises a series of reactions that catabolizes and regenerates methionine. This process is crucial to many cellular functions, including polyamine synthesis, DNA synthesis, redox balance, and DNA and histone methylation. In ... ...

    Abstract The methionine cycle comprises a series of reactions that catabolizes and regenerates methionine. This process is crucial to many cellular functions, including polyamine synthesis, DNA synthesis, redox balance, and DNA and histone methylation. In response to antigens, T cells activate the methionine cycle to support proliferation and differentiation, indicating the importance of the methionine cycle to T cell immunity. In cancer, T cells serve as important effectors of adaptive immunity by directly killing cancerous cells. However, the tumor microenvironment can induce a state of T cell exhaustion by regulating the methionine metabolism of T cells, posing a barrier to both endogenous T cell responses and T cell immunotherapy. Here we review the role of methionine cycle metabolites in regulating the activation and effector function of T cells and explore the mechanism by which tumor cells exploit the methionine pathway as a means of immune evasion. Finally, we discuss new perspectives on reprogramming the methionine cycle of T cells to enhance anti-tumor immunotherapy.
    Language English
    Publishing date 2022-08-10
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.969563
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Metabolic engineering for optimized CAR-T cell therapy.

    McPhedran, Sarah J / Carleton, Gillian A / Lum, Julian J

    Nature metabolism

    2024  Volume 6, Issue 3, Page(s) 396–408

    Abstract: The broad effectiveness of T cell-based therapy for treating solid tumour cancers remains limited. This is partly due to the growing appreciation that immune cells must inhabit and traverse a metabolically demanding tumour environment. Accordingly, ... ...

    Abstract The broad effectiveness of T cell-based therapy for treating solid tumour cancers remains limited. This is partly due to the growing appreciation that immune cells must inhabit and traverse a metabolically demanding tumour environment. Accordingly, recent efforts have centred on using genome-editing technologies to augment T cell-mediated cytotoxicity by manipulating specific metabolic genes. However, solid tumours exhibit numerous characteristics restricting immune cell-mediated cytotoxicity, implying a need for metabolic engineering at the pathway level rather than single gene targets. This emerging concept has yet to be put into clinical practice as many questions concerning the complex interplay between metabolic networks and T cell function remain unsolved. This Perspective will highlight key foundational studies that examine the relevant metabolic pathways required for effective T cell cytotoxicity and persistence in the human tumour microenvironment, feasible strategies for metabolic engineering to increase the efficiency of chimeric antigen receptor T cell-based approaches, and the challenges lying ahead for clinical implementation.
    MeSH term(s) Humans ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/metabolism ; Metabolic Engineering ; Immunotherapy, Adoptive ; Neoplasms/therapy ; Cell- and Tissue-Based Therapy ; Tumor Microenvironment
    Chemical Substances Receptors, Chimeric Antigen
    Language English
    Publishing date 2024-02-22
    Publishing country Germany
    Document type Journal Article ; Review
    ISSN 2522-5812
    ISSN (online) 2522-5812
    DOI 10.1038/s42255-024-00976-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Mass spectrometry imaging methods for visualizing tumor heterogeneity.

    Duncan, Kyle D / Pětrošová, Helena / Lum, Julian J / Goodlett, David R

    Current opinion in biotechnology

    2024  Volume 86, Page(s) 103068

    Abstract: Profiling spatial distributions of lipids, metabolites, and proteins in tumors can reveal unique cellular microenvironments and provide molecular evidence for cancer cell dysfunction and proliferation. Mass spectrometry imaging (MSI) is a label-free ... ...

    Abstract Profiling spatial distributions of lipids, metabolites, and proteins in tumors can reveal unique cellular microenvironments and provide molecular evidence for cancer cell dysfunction and proliferation. Mass spectrometry imaging (MSI) is a label-free technique that can be used to map biomolecules in tumors in situ. Here, we discuss current progress in applying MSI to uncover molecular heterogeneity in tumors. First, the analytical strategies to profile small molecules and proteins are outlined, and current methods for multimodal imaging to maximize biological information are highlighted. Second, we present and summarize biological insights obtained by MSI of tumor tissue. Finally, we discuss important considerations for designing MSI experiments and several current analytical challenges.
    MeSH term(s) Humans ; Mass Spectrometry/methods ; Neoplasms/diagnostic imaging ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Tumor Microenvironment
    Language English
    Publishing date 2024-02-07
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 1052045-4
    ISSN 1879-0429 ; 0958-1669
    ISSN (online) 1879-0429
    ISSN 0958-1669
    DOI 10.1016/j.copbio.2024.103068
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  4. Article ; Online: Decision Aids for Patients With Head and Neck Cancer: Qualitative Elicitation of Design Recommendations From Patient End Users.

    Stringer, Eleah / Lum, Julian J / Livergant, Jonathan / Kushniruk, Andre W

    JMIR human factors

    2023  Volume 10, Page(s) e43551

    Abstract: Background: Patients with head and neck cancer (HNC) carry a clinically significant symptom burden, have alterations in function (eg, impaired ability to chew, swallow, and talk), and decrease in quality of life. Furthermore, treatment impacts social ... ...

    Abstract Background: Patients with head and neck cancer (HNC) carry a clinically significant symptom burden, have alterations in function (eg, impaired ability to chew, swallow, and talk), and decrease in quality of life. Furthermore, treatment impacts social activities and interactions as patients report reduced sexuality and shoulder the highest rates of depression across cancer types. Patients suffer undue anxiety because they find the treatment incomprehensible, which is partially a function of limited, understandable information. Patients' perceptions of having obtained adequate information prior to and during treatment are predictive of positive outcomes. Providing patient-centered decision support and utilizing visual images may increase understanding of treatment options and associated risks to improve satisfaction with their decision and consultation, while reducing decisional conflict.
    Objective: This study aims to gather requirements from survivors of HNC on the utility of key visual components to be used in the design of an electronic decision aid (eDA) to assist with decision-making on treatment options.
    Methods: Informed by a scoping review on eDAs for patients with HNC, screens and visualizations for an eDA were created and then presented to 12 survivors of HNC for feedback on their utility, features, and further requirements. The semistructured interviews were video-recorded and thematically analyzed to inform co-design recommendations.
    Results: A total of 9 themes were organized into 2 categories. The first category, eDAs and decision support, included 3 themes: familiarity with DAs, support of concept, and versatility of the prototype. The second category, evaluation of mock-up, contained 6 themes: reaction to the screens and visualizations, favorite features, complexity, preference for customizability, presentation device, and suggestions for improvement.
    Conclusions: All participants felt an eDA, used in the presence of their oncologist, would support a more thorough and transparent explanation of treatment or augment the quality of education received. Participants liked the simple design of the mock-ups they were shown but, ultimately, desired customizability to adapt the eDA to their individual information needs. This research highlights the value of user-centered design, rooted in acceptability and utility, in medical health informatics, recognizing cancer survivors as the ultimate knowledge holders. This research highlights the value of incorporating visuals into technology-based innovations to engage all patients in treatment decisions.
    Language English
    Publishing date 2023-06-05
    Publishing country Canada
    Document type Journal Article
    ISSN 2292-9495
    ISSN (online) 2292-9495
    DOI 10.2196/43551
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Intermittent Fasting in Cancer: a Role in Survivorship?

    Stringer, Eleah / Lum, Julian J / Macpherson, Nicol

    Current nutrition reports

    2022  Volume 11, Issue 3, Page(s) 500–507

    Abstract: Purpose of review: To discuss the historical development of intermittent fasting, its potential underlying mechanisms, and the state of clinical trials, and to reflect on considerations for practice and future recommendations.: Recent findings: ... ...

    Abstract Purpose of review: To discuss the historical development of intermittent fasting, its potential underlying mechanisms, and the state of clinical trials, and to reflect on considerations for practice and future recommendations.
    Recent findings: Preclinical studies consistently show the robust disease-modifying efficacy of intermittent fasting in various metabolic diseases which may hold implications for cancer prevention and survivorship. Twenty-one clinical trials have or are being conducted on fasting in cancer, utilizing various fasting regimens across different tumor types as a stand-alone intervention or in adjunct to anticancer treatment, with heterogenous outcome variables. Though there are no known, reproducible diets, to cure or prevent cancer recurrence, preliminary research on the underlying mechanisms, tolerance, and safety of intermittent fasting in cancer warrants further investigation. The inherent flexibility of intermittent fasting to accommodate all types of diets is of necessity in oncology.
    MeSH term(s) Fasting ; Humans ; Metabolic Diseases ; Neoplasms ; Survivorship
    Language English
    Publishing date 2022-05-31
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2161-3311
    ISSN (online) 2161-3311
    DOI 10.1007/s13668-022-00425-0
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  6. Article ; Online: Ubiquitinating the way to T cell metabolism.

    McPhedran, Sarah / Lum, Julian J

    The Journal of cell biology

    2022  Volume 221, Issue 7

    Abstract: In this issue, Harris et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202203095) show that phosphofructokinase is a substrate for ubiquitination by Fbxo7, a key protein in the ubiquitination pathway. Their findings point to a new interplay between ...

    Abstract In this issue, Harris et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202203095) show that phosphofructokinase is a substrate for ubiquitination by Fbxo7, a key protein in the ubiquitination pathway. Their findings point to a new interplay between metabolic enzyme degradation in the regulation of T cells.
    MeSH term(s) F-Box Proteins/metabolism ; Humans ; Phosphofructokinases/metabolism ; T-Lymphocytes/metabolism ; Ubiquitination
    Chemical Substances F-Box Proteins ; FBXO7 protein, human ; Phosphofructokinases (EC 2.7.1 -)
    Language English
    Publishing date 2022-06-13
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Comment
    ZDB-ID 218154-x
    ISSN 1540-8140 ; 0021-9525
    ISSN (online) 1540-8140
    ISSN 0021-9525
    DOI 10.1083/jcb.202206006
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  7. Article: Intermittent Fasting in Cancer: a Role in Survivorship?

    Stringer, Eleah / Lum, Julian J. / Macpherson, Nicol

    Current nutrition reports. 2022 Sept., v. 11, no. 3

    2022  

    Abstract: PURPOSE OF REVIEW: To discuss the historical development of intermittent fasting, its potential underlying mechanisms, and the state of clinical trials, and to reflect on considerations for practice and future recommendations. RECENT FINDINGS: ... ...

    Abstract PURPOSE OF REVIEW: To discuss the historical development of intermittent fasting, its potential underlying mechanisms, and the state of clinical trials, and to reflect on considerations for practice and future recommendations. RECENT FINDINGS: Preclinical studies consistently show the robust disease-modifying efficacy of intermittent fasting in various metabolic diseases which may hold implications for cancer prevention and survivorship. Twenty-one clinical trials have or are being conducted on fasting in cancer, utilizing various fasting regimens across different tumor types as a stand-alone intervention or in adjunct to anticancer treatment, with heterogenous outcome variables. Though there are no known, reproducible diets, to cure or prevent cancer recurrence, preliminary research on the underlying mechanisms, tolerance, and safety of intermittent fasting in cancer warrants further investigation. The inherent flexibility of intermittent fasting to accommodate all types of diets is of necessity in oncology.
    Keywords cancer recurrence ; fasting ; neoplasms ; survival rate
    Language English
    Dates of publication 2022-09
    Size p. 500-507.
    Publishing place Springer US
    Document type Article
    Note Review
    ISSN 2161-3311
    DOI 10.1007/s13668-022-00425-0
    Database NAL-Catalogue (AGRICOLA)

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  8. Article ; Online: Strategies for uncovering stable isotope tracing patterns between cell populations.

    MacPherson, Sarah / Duncan, Kyle D / Goodlett, David R / Lum, Julian J

    Current opinion in biotechnology

    2023  Volume 83, Page(s) 102991

    Abstract: Despite practical complexities, isotope tracing studies in humans are becoming increasingly feasible. However, several technological challenges need to be addressed in order to take full advantage of human tracing studies. First, absolute metabolic flux ... ...

    Abstract Despite practical complexities, isotope tracing studies in humans are becoming increasingly feasible. However, several technological challenges need to be addressed in order to take full advantage of human tracing studies. First, absolute metabolic flux measurements in mice are not so easily applied to human models, given that tissue resection is restricted to a single surgical time point. Second, isotope tracing has yet to be employed to detect metabolic differences between cells types in vivo. Here, we discuss the current models and propose an alternative, liquid tumor environment, that could overcome these limitations. Furthermore, we highlight current strategies used to maintain isotopolog enrichment following cell isolation techniques to facilitate cell-type-specific analysis.
    MeSH term(s) Animals ; Humans ; Mice ; Isotopes ; Isotope Labeling
    Chemical Substances Isotopes
    Language English
    Publishing date 2023-08-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 1052045-4
    ISSN 1879-0429 ; 0958-1669
    ISSN (online) 1879-0429
    ISSN 0958-1669
    DOI 10.1016/j.copbio.2023.102991
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  9. Article: PSMA imaging as a non-invasive tool to monitor inducible gene expression in vivo.

    Simunic, Marin / Joshi, Jay T / Merkens, Helen / Colpo, Nadine / Kuo, Hsiou-Ting / Lum, Julian J / Bénard, François

    EJNMMI research

    2024  Volume 14, Issue 1, Page(s) 3

    Language English
    Publishing date 2024-01-04
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 2619892-7
    ISSN 2191-219X
    ISSN 2191-219X
    DOI 10.1186/s13550-023-01063-5
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  10. Article ; Online: Autophagy metabolically suppresses CD8

    Carleton, Gillian / Lum, Julian J

    Autophagy

    2019  Volume 15, Issue 9, Page(s) 1648–1649

    Abstract: Macroautophagy/autophagy is a critical regulator of adaptive T cell immunity and homeostasis. However, the role of T cell autophagy in regulating antitumor immune responses is less clear. In a recent study, we showed that deletion of the essential ... ...

    Abstract Macroautophagy/autophagy is a critical regulator of adaptive T cell immunity and homeostasis. However, the role of T cell autophagy in regulating antitumor immune responses is less clear. In a recent study, we showed that deletion of the essential autophagy genes
    MeSH term(s) Animals ; Autophagy/genetics ; Autophagy/immunology ; Autophagy-Related Protein 5/genetics ; Autophagy-Related Protein 5/metabolism ; Autophagy-Related Proteins/genetics ; Autophagy-Related Proteins/metabolism ; Bone Marrow Transplantation ; CD8-Positive T-Lymphocytes/immunology ; Cell Line, Tumor ; Glucose/metabolism ; Histones/chemistry ; Histones/metabolism ; Interferon-gamma/metabolism ; Methylation ; Mice ; Mice, Knockout ; Neoplasms/immunology ; Tumor Necrosis Factor-alpha/metabolism ; Vesicular Transport Proteins/genetics ; Vesicular Transport Proteins/metabolism
    Chemical Substances Atg14 protein, mouse ; Atg5 protein, mouse ; Autophagy-Related Protein 5 ; Autophagy-Related Proteins ; Histones ; Tumor Necrosis Factor-alpha ; Vesicular Transport Proteins ; Interferon-gamma (82115-62-6) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2019-06-14
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2454135-7
    ISSN 1554-8635 ; 1554-8627
    ISSN (online) 1554-8635
    ISSN 1554-8627
    DOI 10.1080/15548627.2019.1628545
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