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  1. Article ; Online: You are what you eat: How to best fuel your immune system.

    Hellmich, Charlotte / Wojtowicz, Edyta E

    Frontiers in immunology

    2022  Volume 13, Page(s) 1003006

    Abstract: Normal bone marrow (BM) homeostasis ensures consistent production of progenitor cells and mature blood cells. This requires a reliable supply of nutrients in particular free fatty acids, carbohydrates and protein. Furthermore, rapid changes can occur in ... ...

    Abstract Normal bone marrow (BM) homeostasis ensures consistent production of progenitor cells and mature blood cells. This requires a reliable supply of nutrients in particular free fatty acids, carbohydrates and protein. Furthermore, rapid changes can occur in response to stress such as infection which can alter the demand for each of these metabolites. In response to infection the haematopoietic stem cells (HSCs) must respond and expand rapidly to facilitate the process of emergency granulopoiesis required for the immediate immune response. This involves a shift from the use of glycolysis to oxidative phosphorylation for energy production and therefore an increased demand for metabolites. Thus, the right balance of each dietary component helps to maintain not only normal homeostasis but also the ability to quickly respond to systemic stress. In addition, some dietary components can drive chronic inflammatory changes in the absence of infection or immune stress, which in turn can impact on overall immune function. The optimal nutrition for the best immunological outcomes would therefore be a diet that supports the functions of immune cells allowing them to initiate effective responses against pathogens but also to resolve the response rapidly when necessary and to avoid any underlying chronic inflammation. In this review we discuss how these key dietary components can alter immune function, what is their impact on bone marrow metabolism and how changes in dietary intake of each of these can improve the outcomes of infections.
    MeSH term(s) Bone Marrow ; Carbohydrates ; Fatty Acids, Nonesterified/metabolism ; Hematopoiesis ; Hematopoietic Stem Cells/metabolism
    Chemical Substances Carbohydrates ; Fatty Acids, Nonesterified
    Language English
    Publishing date 2022-09-20
    Publishing country Switzerland
    Document type Journal Article ; Review ; Research Support, Non-U.S. Gov't
    ZDB-ID 2606827-8
    ISSN 1664-3224 ; 1664-3224
    ISSN (online) 1664-3224
    ISSN 1664-3224
    DOI 10.3389/fimmu.2022.1003006
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: BCL-2 inhibition in haematological malignancies: Clinical application and complications.

    Fowler-Shorten, Dominic J / Hellmich, Charlotte / Markham, Matthew / Bowles, Kristian M / Rushworth, Stuart A

    Blood reviews

    2024  Volume 65, Page(s) 101195

    Abstract: B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent ... ...

    Abstract B-cell lymphoma-2 (BCL-2) family proteins are fundamental regulators of the intrinsic apoptotic pathway which modulate cellular fate. In many haematological malignancies, overexpression of anti-apoptotic factors (BCL-2, BCL-XL and MCL-1) circumvent apoptosis. To address this cancer hallmark, a concerted effort has been made to induce apoptosis by inhibiting BCL-2 family proteins. A series of highly selective BCL-2 homology 3 (BH3) domain mimetics are in clinical use and in ongoing clinical trials for acute myeloid leukaemia (AML), chronic myeloid leukaemia (CML), chronic lymphocytic leukaemia (CLL), and multiple myeloma (MM). These inhibitors serve as promising candidates, both as single agents or in combination therapy to improve patient outcomes. In other diseases such as follicular lymphoma, efficacy has been notably limited. There are also clinical problems with BCL-2 family inhibition, including drug resistance, disease relapse, tumour lysis syndrome, and clinically relevant cytopenias. Here, we provide a balanced view on both the clinical benefits of BCL-2 inhibition as well as the associated challenges.
    MeSH term(s) Humans ; Neoplasm Recurrence, Local/drug therapy ; Hematologic Neoplasms/metabolism ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Apoptosis ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use
    Chemical Substances Proto-Oncogene Proteins c-bcl-2 ; Antineoplastic Agents
    Language English
    Publishing date 2024-03-21
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 639015-8
    ISSN 1532-1681 ; 0268-960X
    ISSN (online) 1532-1681
    ISSN 0268-960X
    DOI 10.1016/j.blre.2024.101195
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Acute Myeloid Leukaemia Drives Metabolic Changes in the Bone Marrow Niche.

    Maynard, Rebecca S / Hellmich, Charlotte / Bowles, Kristian M / Rushworth, Stuart A

    Frontiers in oncology

    2022  Volume 12, Page(s) 924567

    Abstract: Acute myeloid leukaemia (AML) is a highly proliferative cancer characterised by infiltration of immature haematopoietic cells in the bone marrow (BM). AML predominantly affects older people and outcomes, particularly in this difficult to treat population ...

    Abstract Acute myeloid leukaemia (AML) is a highly proliferative cancer characterised by infiltration of immature haematopoietic cells in the bone marrow (BM). AML predominantly affects older people and outcomes, particularly in this difficult to treat population remain poor, in part due to inadequate response to therapy, and treatment toxicity. Normal haematopoiesis is supported by numerous support cells within the BM microenvironment or niche, including adipocytes, stromal cells and endothelial cells. In steady state haematopoiesis, haematopoietic stem cells (HSCs) primarily acquire ATP through glycolysis. However, during stress-responses HSCs rapidly transition to oxidative phosphorylation, enabled by mitochondrial plasticity. Historically it was thought that cancer cells preferentially used glycolysis for ATP production, however recently it has become evident that many cancers, including AML primarily use the TCA cycle and oxidative phosphorylation for rapid proliferation. AML cells hijack the stress-response pathways of their non-malignant counterparts, utilising mitochondrial changes to drive expansion. In addition, amino acids are also utilised by leukaemic stem cells to aid their metabolic output. Together, these processes allow AML cells to maximise their ATP production, using multiple metabolites and fuelling rapid cell turnover which is a hallmark of the disease. This review of AML derived changes in the BM niche, which enable enhanced metabolism, will consider the important pathways and discuss future challenges with a view to understanding how AML cells are able to hijack metabolic pathways and how we may elucidate new targets for potential therapies.
    Language English
    Publishing date 2022-06-29
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2022.924567
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: ARQ531: the therapy that targets multiple pathways in acute myeloid leukemia.

    Hellmich, Charlotte / Bowles, Kristian / Rushworth, Stuart

    Haematologica

    2020  Volume 105, Issue 10, Page(s) 2350–2352

    MeSH term(s) Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; Protein Kinase Inhibitors
    Chemical Substances Protein Kinase Inhibitors
    Language English
    Publishing date 2020-10-01
    Publishing country Italy
    Document type Editorial ; Comment
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2020.257022
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Outpatient parenteral antimicrobial therapy (OPAT) in Germany: insights and clinical outcomes from the K-APAT cohort study.

    Schmidt-Hellerau, Kirsten / Baade, Nina / Günther, Marina / Scholten, Nadine / Lindemann, Christoph Heinrich / Leisse, Charlotte / Oberröhrmann, Charlotte / Peter, Sophie / Jung, Norma / Suarez, Isabelle / Horn, Carola / Ihle, Peter / Küpper-Nybelen, Jutta / Hagemeier, Anna / Hellmich, Martin / Lehmann, Clara

    Infection

    2024  

    Abstract: Purpose: Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and ... ...

    Abstract Purpose: Outpatient parenteral antimicrobial therapy (OPAT) offers several key advantages, including enhanced patient quality of life, reduced healthcare costs, and a potential reduction of nosocomial infections. It is acknowledged for its safety and effectiveness. This study provides the first systematic clinical data for Germany, where OPAT has not yet been widely adopted. The aim is to establish a foundational reference point for further research and integration of OPAT into the German healthcare system.
    Methods: This prospective observational study descriptively analyses data obtained from a cohort of patients receiving OPAT. Both in- and outpatients from all medical specialties could be recruited. Patients administered the anti-infective medications themselves at home using elastomeric pumps.
    Results: 77 patients received OPAT, with a median duration of 15 days and saving 1782 inpatient days. The most frequently treated entities were orthopaedic infections (n = 20, 26%), S. aureus bloodstream infection (n = 16, 21%) and infectious endocarditis (n = 11, 14%). The most frequently applied drugs were flucloxacillin (n = 18, 23%), penicillin G (n = 13, 17%) and ceftriaxone (n = 10; 13%). Only 5% of patients (n = 4) reported to have missed more than one outpatient dose (max. 3 per patient). Only one catheter-related adverse event required medical intervention, and there were no catheter-related infections.
    Conclusion: The study demonstrates that OPAT can be safely conducted in Germany. In preparation for its broader implementation, crucial next steps include creating medical guidelines, fostering interdisciplinary and inter-sectoral communication, as well as creating financial and structural regulations that facilitate and encourage the adoption of OPAT.
    Trial registration number: NCT04002453.
    Language English
    Publishing date 2024-03-13
    Publishing country Germany
    Document type Journal Article
    ZDB-ID 185104-4
    ISSN 1439-0973 ; 0300-8126 ; 0173-2129
    ISSN (online) 1439-0973
    ISSN 0300-8126 ; 0173-2129
    DOI 10.1007/s15010-024-02199-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Acute myeloid leukemia-driven IL-3-dependent upregulation of BCL2 in non-malignant hematopoietic stem and progenitor cells increases venetoclax-induced cytopenias.

    Fowler-Shorten, Dominic J / Maynard, Rebecca S / Hampton, Katherine / Altera, Annalisa / Markham, Matthew / Ehikioya, Martha / Wojtowicz, Edyta E / Bowles, Kristian M / Rushworth, Stuart A / Hellmich, Charlotte

    Haematologica

    2024  Volume 109, Issue 5, Page(s) 1576–1581

    MeSH term(s) Humans ; Leukemia, Myeloid, Acute/metabolism ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/pathology ; Sulfonamides/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/drug effects ; Interleukin-3/metabolism ; Up-Regulation/drug effects ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Cytopenia
    Chemical Substances venetoclax (N54AIC43PW) ; Sulfonamides ; Bridged Bicyclo Compounds, Heterocyclic ; Proto-Oncogene Proteins c-bcl-2 ; Interleukin-3 ; BCL2 protein, human ; Antineoplastic Agents ; IL3 protein, human
    Language English
    Publishing date 2024-05-01
    Publishing country Italy
    Document type Letter ; Research Support, Non-U.S. Gov't ; Journal Article
    ZDB-ID 2333-4
    ISSN 1592-8721 ; 0017-6567 ; 0390-6078
    ISSN (online) 1592-8721
    ISSN 0017-6567 ; 0390-6078
    DOI 10.3324/haematol.2023.283944
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Across the world availability of flavour accessories for tobacco products.

    Havermans, Anne / Pauwels, Charlotte G G M / Bakker-'t Hart, Ingrid M E / Fayokun, Ranti / van Nierop, Lotte E / Hellmich, Ina M / Talhout, Reinskje

    Tobacco control

    2024  

    Abstract: Objective: This study aimed to provide an inventory of different types of flavour accessories for combustible tobacco products in eight countries varying in their approaches to flavour legislation and cultural aspects, including tobacco use.: Methods!# ...

    Abstract Objective: This study aimed to provide an inventory of different types of flavour accessories for combustible tobacco products in eight countries varying in their approaches to flavour legislation and cultural aspects, including tobacco use.
    Methods: A standardised search protocol was developed and shared with local informants to acquire information on the availability and marketing of flavour accessories in web shops accessible from Brazil, India, Italy, Singapore, South Africa, Switzerland, the UK and the USA. Characteristics of the products and web shops were reported, and flavours were categorised in a flavour wheel.
    Results: Flavour accessories were available in all participating countries. Reported types are flavour capsules, cards, filter tips and tubes for make-your-own cigarettes, drops, sprays, rolling paper, aroma markers, a flavour stone and a flavour powder. In total, 118 unique flavours were reported, which were mostly fruity and sweet. Marketing of these products was often associated with (menthol) flavour bans.
    Conclusions: The wide availability and variety of flavour accessories raise significant public health concerns, as they have attractive flavours, and thus hinder the regulatory aim of flavour bans. Flavour accessories are not tobacco products and thus not regulated as such. Therefore, it is recommended that policymakers include these products in comprehensive flavour bans, to close this loophole in existing tobacco control measures.
    Language English
    Publishing date 2024-04-05
    Publishing country England
    Document type Journal Article
    ZDB-ID 1146554-2
    ISSN 1468-3318 ; 0964-4563
    ISSN (online) 1468-3318
    ISSN 0964-4563
    DOI 10.1136/tc-2023-058255
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Bone Marrow Senescence and the Microenvironment of Hematological Malignancies.

    Hellmich, Charlotte / Moore, Jamie A / Bowles, Kristian M / Rushworth, Stuart A

    Frontiers in oncology

    2020  Volume 10, Page(s) 230

    Abstract: Senescence is the irreversible arrest of cell proliferation that has now been shown to play an important role in both health and disease. With increasing age senescent cells accumulate throughout the body, including the bone marrow and this has been ... ...

    Abstract Senescence is the irreversible arrest of cell proliferation that has now been shown to play an important role in both health and disease. With increasing age senescent cells accumulate throughout the body, including the bone marrow and this has been associated with a number of age-related pathologies including malignancies. It has been shown that the senescence associated secretory phenotype (SASP) creates a pro-tumoural environment that supports proliferation and survival of malignant cells. Understanding the role of senescent cells in tumor development better may help us to identify new treatment targets to impair tumor survival and reduce treatment resistance. In this review, we will specifically discuss the role of senescence in the aging bone marrow (BM) microenvironment. Many BM disorders are age-related diseases and highly dependent on the BM microenvironment. Despite advances in drug development the prognosis particularly for older patients remains poor and new treatment approaches are needed to improve outcomes for patients. In this review, we will focus on the relationship of senescence and hematological malignancies, how senescence promotes cancer development and how malignant cells induce senescence.
    Language English
    Publishing date 2020-02-25
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2649216-7
    ISSN 2234-943X
    ISSN 2234-943X
    DOI 10.3389/fonc.2020.00230
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Unstructural Biology of TRP Ion Channels: The Role of Intrinsically Disordered Regions in Channel Function and Regulation.

    Goretzki, Benedikt / Guhl, Charlotte / Tebbe, Frederike / Harder, Jean-Martin / Hellmich, Ute A

    Journal of molecular biology

    2021  Volume 433, Issue 17, Page(s) 166931

    Abstract: The first genuine high-resolution single particle cryo-electron microscopy structure of a membrane protein determined was a transient receptor potential (TRP) ion channel, TRPV1, in 2013. This methodical breakthrough opened up a whole new world for ... ...

    Abstract The first genuine high-resolution single particle cryo-electron microscopy structure of a membrane protein determined was a transient receptor potential (TRP) ion channel, TRPV1, in 2013. This methodical breakthrough opened up a whole new world for structural biology and ion channel aficionados alike. TRP channels capture the imagination due to the sheer endless number of tasks they carry out in all aspects of animal physiology. To date, structures of at least one representative member of each of the six mammalian TRP channel subfamilies as well as of a few non-mammalian families have been determined. These structures were instrumental for a better understanding of TRP channel function and regulation. However, all of the TRP channel structures solved so far are incomplete since they miss important information about highly flexible regions found mostly in the channel N- and C-termini. These intrinsically disordered regions (IDRs) can represent between a quarter to almost half of the entire protein sequence and act as important recruitment hubs for lipids and regulatory proteins. Here, we analyze the currently available TRP channel structures with regard to the extent of these "missing" regions and compare these findings to disorder predictions. We discuss select examples of intra- and intermolecular crosstalk of TRP channel IDRs with proteins and lipids as well as the effect of splicing and post-translational modifications, to illuminate their importance for channel function and to complement the prevalently discussed structural biology of these versatile and fascinating proteins with their equally relevant 'unstructural' biology.
    MeSH term(s) Animals ; Cryoelectron Microscopy/methods ; Humans ; Lipids/chemistry ; Mammals/metabolism ; Protein Processing, Post-Translational/physiology ; Proteins/metabolism ; RNA Splicing/physiology ; Transient Receptor Potential Channels/metabolism
    Chemical Substances Lipids ; Proteins ; Transient Receptor Potential Channels
    Language English
    Publishing date 2021-03-16
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 80229-3
    ISSN 1089-8638 ; 0022-2836
    ISSN (online) 1089-8638
    ISSN 0022-2836
    DOI 10.1016/j.jmb.2021.166931
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Outpatient parenteral antimicrobial therapy in Germany: a prospective cohort study protocol.

    Scholten, Nadine / Leisse, Charlotte / Brandes, Vanessa / Oberröhrmann, Charlotte / Ihle, Peter / Peter, Sophie / Hagemeier, Anna / Hellmich, Martin / Lindemann, Christoph H / Samel, Christina / Pfaff, Holger / Lehmann, Clara

    BMJ open

    2022  Volume 12, Issue 11, Page(s) e061417

    Abstract: Introduction: Outpatient parenteral antimicrobial therapy (OPAT) means intravenous administration of antibiotics outside the hospital. The antibiotics are administered at the patient's home. The advantages are the shortening of the inpatient stay, which ...

    Abstract Introduction: Outpatient parenteral antimicrobial therapy (OPAT) means intravenous administration of antibiotics outside the hospital. The antibiotics are administered at the patient's home. The advantages are the shortening of the inpatient stay, which means that patients can remain in their familiar environment, the reduction of nosocomial infections as well as the reduction of hospital and therapy costs. Nevertheless, OPAT is rarely performed in Germany, despite its international application. Therefore, systematic data on OPAT are not available in Germany. The project objective is to investigate the medical care using OPAT under medical, epidemiological and economic aspects within the framework of the Cologne Network of Infectious Diseases.
    Methods and analysis: Observational study with mixed-methods approach, qualitative analysis to identify physician-side factors to assess the attitude of general practitioners in Cologne with regard to possible implementation barriers of an OPAT. Longitudinal analysis of an OPAT patient cohort with respect to clinical and patient-relevant outcomes using descriptive and conclusive statistics.
    Ethics and dissemination: The study has been approved by the Institutional Review Board of the University of Cologne, Germany (19-1284-1). Written informed consent was obtained from all participants. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.
    Trial registration number: NCT04002453.
    MeSH term(s) Humans ; Outpatients ; Prospective Studies ; Anti-Infective Agents/therapeutic use ; Anti-Bacterial Agents/therapeutic use ; Ambulatory Care/methods ; Germany ; Observational Studies as Topic
    Chemical Substances Anti-Infective Agents ; Anti-Bacterial Agents
    Language English
    Publishing date 2022-11-14
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2022-061417
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