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  1. Article: Deciphering the molecular biology of inflammatory breast cancer through molecular characterization of patient samples and preclinical models.

    Rypens, Charlotte / Van Berckelaer, Christophe / Berditchevski, Fedor / van Dam, Peter / Van Laere, Steven

    International review of cell and molecular biology

    2024  Volume 384, Page(s) 77–112

    Abstract: Inflammatory breast cancer is an aggressive subtype of breast cancer with dismal patient prognosis and a unique clinical presentation. In the past two decades, molecular profiling technologies have been used in order to gain insight into the molecular ... ...

    Abstract Inflammatory breast cancer is an aggressive subtype of breast cancer with dismal patient prognosis and a unique clinical presentation. In the past two decades, molecular profiling technologies have been used in order to gain insight into the molecular biology of IBC and to search for possible targets for treatment. Although a gene signature that accurately discriminates between IBC and nIBC patient samples and preclinical models was identified, the overall genomic and transcriptomic differences are small and ambiguous, mainly due to the limited sample sizes of the evaluated patient series and the failure to correct for confounding effects of the molecular subtypes. Nevertheless, data collected over the past 20 years by independent research groups increasingly support the existence of several IBC-specific biological characteristics. In this review, these features are classified as established, emerging and conceptual hallmarks based on the level of evidence reported in the literature. In addition, a synoptic model is proposed that integrates all hallmarks and that can explain how cancer cell intrinsic mechanisms (i.e. NF-κB activation, genomic instability, MYC-addiction, TGF-β resistance, adaptive stress response, chromatin remodeling, epithelial-to-mesenchymal transition) can contribute to the establishment of the dynamic immune microenvironment associated with IBC. It stands to reason that future research projects are needed to further refine (parts of) this model and to investigate its clinical translatability.
    MeSH term(s) Humans ; Female ; Inflammatory Breast Neoplasms/genetics ; Breast Neoplasms/genetics ; Gene Expression Profiling ; Transcriptome ; Gene Expression Regulation, Neoplastic ; Molecular Biology ; Tumor Microenvironment
    Language English
    Publishing date 2024-02-10
    Publishing country Netherlands
    Document type Review ; Journal Article
    ZDB-ID 2427220-6
    ISSN 1937-6448 ; 0074-7696
    ISSN 1937-6448 ; 0074-7696
    DOI 10.1016/bs.ircmb.2023.10.006
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  2. Article: Genomic landscape of inflammatory breast cancer identifies potential actionable genetic alterations.

    Bertucci, François / Van Laere, Steven / Birnbaum, Daniel

    Oncoscience

    2020  Volume 7, Issue 7-8, Page(s) 57–59

    Language English
    Publishing date 2020-06-30
    Publishing country United States
    Document type Journal Article
    ISSN 2331-4737
    ISSN 2331-4737
    DOI 10.18632/oncoscience.515
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  3. Article: Association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms in giant cell arteritis.

    Blockmans, Daniel / Moreel, Lien / Betrains, Albrecht / Vanderschueren, Steven / Coudyzer, Walter / Boeckxstaens, Lennert / Van Laere, Koen

    Frontiers in medicine

    2024  Volume 11, Page(s) 1384533

    Abstract: Background: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular ... ...

    Abstract Background: A positive PET scan at diagnosis was associated with a greater yearly increase in ascending and descending aortic diameter and thoracic aortic volume in patients with giant cell arteritis (GCA). Radiologic and histopathologic vascular abnormalities persist in a subset of treated patients despite clinical remission. The aim of this study was to evaluate the association between vascular FDG uptake during follow-up and the development of thoracic aortic aneurysms.
    Methods: We recently performed a prospective cohort study of 106 GCA patients, who underwent FDG PET and CT imaging at diagnosis and CT imaging yearly for a maximum of 10 years. In this
    Results: Eighty-eight repeat PET scans were performed in 52 out of 106 GCA patients, who were included in the original prospective cohort. Fifty-five (63%) PET scans were done at the time of a relapse and 33 (38%) were done while in remission. Nine out of ten patients with an incident thoracic aortic aneurysm had both a positive PET scan at diagnosis and during follow-up.
    Conclusion: In addition to the intensity and extent of the initial vascular inflammation, ongoing aortic inflammation may contribute to the development of thoracic aortic aneurysms in GCA. However, this hypothesis should be confirmed in a large prospective trial with repeat PET scans at predefined time points during follow-up.
    Language English
    Publishing date 2024-03-20
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2775999-4
    ISSN 2296-858X
    ISSN 2296-858X
    DOI 10.3389/fmed.2024.1384533
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  4. Article ; Online: Prevalence, characteristics, and outcome of subclinical vasculitis in polymyalgia rheumatica: a retrospective cohort study.

    Moreel, Lien / Boeckxstaens, Lennert / Betrains, Albrecht / Smans, Timo / Molenberghs, Geert / Van Laere, Koen / De Langhe, Ellen / Vanderschueren, Steven / Blockmans, Daniel

    Rheumatology (Oxford, England)

    2024  

    Abstract: Objectives: Two recent meta-analyses reported subclinical vasculitis in 22-23% of patients with polymyalgia rheumatica (PMR). We aimed to evaluate the prevalence, characteristics, and outcome of subclinical vasculitis among our PMR patients.: Methods!# ...

    Abstract Objectives: Two recent meta-analyses reported subclinical vasculitis in 22-23% of patients with polymyalgia rheumatica (PMR). We aimed to evaluate the prevalence, characteristics, and outcome of subclinical vasculitis among our PMR patients.
    Methods: Consecutive patients with GCA/PMR spectrum disease with isolated PMR symptoms who underwent FDG PET imaging between 2003-2020 and who were followed for ≥6 months, were included retrospectively. Vasculitis was defined as FDG uptake ≥ grade 2 in any vessel.
    Results: We included 337 patients, of whom 31 (9%) with subclinical vasculitis. Among those with subclinical vasculitis, 21 (58%) had isolated large vessel vasculitis, 3 (10%) had isolated cranial vasculitis and 7 (23%) had both cranial and large vessel vasculitis. The glucocorticoid (GC) starting dose and GC doses during follow-up were higher in those with subclinical vasculitis until 12 months after diagnosis (p< 0.001). There was no difference in the duration of GC treatment (25 vs 20 months, p= 0.187). Cox proportional hazard regression analyses showed no difference in the proportion of patients able to stop GC (HR 0.78 [95% CI 0.49-1.25], p= 0.303) and in the proportion of patients with relapse (HR 0.82 [95%CI 0.50-1.36], p= 0.441).
    Conclusion: Only 9% of our PMR patients had subclinical vasculitis with a predilection for large vessel vasculitis. There were no differences in relapse rate and duration of GC treatment, however those with subclinical vasculitis received higher GC doses until 12 months after diagnosis. Prospective interventional trials are needed to evaluate the outcome of PMR patients with and without subclinical vasculitis treated with similar GC protocol.
    Language English
    Publishing date 2024-03-28
    Publishing country England
    Document type Journal Article
    ZDB-ID 1464822-2
    ISSN 1462-0332 ; 1462-0324
    ISSN (online) 1462-0332
    ISSN 1462-0324
    DOI 10.1093/rheumatology/keae208
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  5. Article ; Online: First report of a prosthetic joint infection with Fannyhessea (Atopobium) vaginae.

    Massa, Bo / De Laere, Emmanuel / Raes, Rik / Vervaeke, Steven / Van Hoecke, Frederik

    European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology

    2022  Volume 41, Issue 7, Page(s) 1023–1027

    Abstract: This case describes a 77-year-old woman with dysregulated type II diabetes, presenting with a prosthetic joint infection and bacteremia. Computed tomography (CT) of the pelvis and sacrum revealed manifest periprosthetic collections, suggestive of a ... ...

    Abstract This case describes a 77-year-old woman with dysregulated type II diabetes, presenting with a prosthetic joint infection and bacteremia. Computed tomography (CT) of the pelvis and sacrum revealed manifest periprosthetic collections, suggestive of a septic arthritis with loosening of the hip prosthesis. Synovial fluid grew Fannyhessea vaginae, identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). To our knowledge, this is the first report of a prosthetic joint infection due to this organism.
    MeSH term(s) Actinobacteria ; Actinomycetaceae ; Aged ; Arthritis, Infectious/diagnosis ; Arthritis, Infectious/drug therapy ; Bacteremia/diagnosis ; Bacteremia/microbiology ; Diabetes Mellitus, Type 2 ; Female ; Humans ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods
    Language English
    Publishing date 2022-05-24
    Publishing country Germany
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 603155-9
    ISSN 1435-4373 ; 0934-9723 ; 0722-2211
    ISSN (online) 1435-4373
    ISSN 0934-9723 ; 0722-2211
    DOI 10.1007/s10096-022-04461-0
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  6. Article: XIAP overexpressing inflammatory breast cancer patients have high infiltration of immunosuppressive subsets and increased TNFR1 signaling targetable with Birinapant.

    Van Berckelaer, Christophe / Van Laere, Steven / Lee, Seayoung / Morse, Michael A / Geradts, Joseph / Dirix, Luc / Kockx, Mark / Bertucci, François / Van Dam, Peter / Devi, Gayathri R

    Translational oncology

    2024  Volume 43, Page(s) 101907

    Abstract: Objective: To assess the expression pattern of X-linked inhibitor of apoptosis protein (XIAP), a cellular stress sensor, and delineate the associated changes in the tumor immune microenvironment (TiME) for prognostic value and new therapeutic targets in ...

    Abstract Objective: To assess the expression pattern of X-linked inhibitor of apoptosis protein (XIAP), a cellular stress sensor, and delineate the associated changes in the tumor immune microenvironment (TiME) for prognostic value and new therapeutic targets in inflammatory breast cancer (IBC).
    Methods: Immunohistochemistry was conducted to assess the spatial localization of immune subsets, XIAP, and PDL1 expression in IBC and non-inflammatory breast cancer (nIBC) pretreatment tumors (n = 142). Validation and further exploration were performed by gene expression analysis of patient tumors along with signaling studies in a co-culture model.
    Results: High XIAP in 37/81 IBC patients correlated significantly with high PD-L1, increased infiltration of FOXP3+ Tregs, CD163+ tumor-associated macrophages (TAMs), low CD8/CD163 ratio in both tumor stroma (TS) and invasive margins (IM), and higher CD8+ T cells and CD79α+ B cells in the IM. Gene set enrichment analysis identified cellular stress response- and inflammation-related genes along with tumor necrosis factor receptor 1 (TNFR1) expression in high-XIAP IBC tumors. Induction of TNFR1 and XIAP was observed when patient-derived SUM149 IBC cells were co-cultured with human macrophage-conditioned media simulating TAMs, further demonstrating that the TNF-α signaling pathway is a likely candidate governing TAM-induced XIAP overexpression in IBC cells. Finally, addition of Birinapant, a pan IAP antagonist, induced cell death in the pro-survival cytokine-enriched conditions.
    Conclusion: Using immunophenotyping and gene expression analysis in patient biospecimens along with in silico modeling and a preclinical model with a pan-IAP antagonist, this study revealed an interplay between increased TAMs, TNF-α signaling, and XIAP activation during (immune) stress in IBC. These data demonstrate the potential of IAP antagonists as immunomodulators for improving IBC therapeutic regimens.
    Language English
    Publishing date 2024-02-27
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2443840-6
    ISSN 1936-5233
    ISSN 1936-5233
    DOI 10.1016/j.tranon.2024.101907
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  7. Article: Clinical implications of fever at diagnosis in polymyalgia rheumatica: an age- and sex-matched case control study of 120 patients.

    Betrains, Albrecht / Boeckxstaens, Lennert / Van Laere, Koen / Vanderschueren, Steven / Blockmans, Daniel

    Clinical and experimental rheumatology

    2021  Volume 40, Issue 1, Page(s) 193–194

    MeSH term(s) Case-Control Studies ; Diagnosis, Differential ; Fever/diagnosis ; Fever/epidemiology ; Fever/etiology ; Giant Cell Arteritis/diagnosis ; Humans ; Polymyalgia Rheumatica/diagnosis ; Polymyalgia Rheumatica/epidemiology
    Language English
    Publishing date 2021-07-24
    Publishing country Italy
    Document type Letter
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    DOI 10.55563/clinexprheumatol/6z2rdg
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  8. Article: Clinical implications of fever at diagnosis in polymyalgia rheumatica: an age- and sex-matched case control study of 120 patients. Reply to Milchert et al. and Manzo et al.

    Betrains, Albrecht / Boeckxstaens, Lennert / Van Laere, Koen / Vanderschueren, Steven / Blockmans, Daniel

    Clinical and experimental rheumatology

    2021  Volume 40, Issue 3, Page(s) 668

    MeSH term(s) Case-Control Studies ; Fever ; Giant Cell Arteritis/diagnosis ; Humans ; Polymyalgia Rheumatica/diagnosis
    Language English
    Publishing date 2021-11-03
    Publishing country Italy
    Document type Letter ; Comment
    ZDB-ID 605886-3
    ISSN 1593-098X ; 0392-856X
    ISSN (online) 1593-098X
    ISSN 0392-856X
    DOI 10.55563/clinexprheumatol/6uezpq
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  9. Article ; Online: Higher diagnostic yield of 18F-FDG PET in inflammation of unknown origin compared to fever of unknown origin.

    Betrains, Albrecht / Boeckxstaens, Lennert / Moreel, Lien / Wright, William F / Blockmans, Daniel / Van Laere, Koen / Vanderschueren, Steven

    European journal of internal medicine

    2023  Volume 110, Page(s) 71–76

    Abstract: Objective: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an important imaging technique in the workup of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Studies comparing the diagnostic yield of 18F-FDG PET ...

    Abstract Objective: 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) is an important imaging technique in the workup of fever of unknown origin (FUO) and inflammation of unknown origin (IUO). Studies comparing the diagnostic yield of 18F-FDG PET between both entities are lacking.
    Methods: Retrospective analysis of FUO/IUO patients who underwent 18F-FDG PET between 2000 and 2019 in the University Hospitals of Leuven (Belgium). 18F-FDG PET images were assessed for accuracy and contribution towards the final diagnosis. Logistic regression was performed to evaluate the association between meeting FUO or IUO criteria and diagnostic contribution of 18F-FDG PET with and without adjustment for confounders.
    Results: Out of 604 patients, 439 (73%, mean age 56 years, 43% female) underwent 18F-FDG PET imaging, including 349 (79%) classified as FUO and 90 (21%) as IUO. Noninfectious inflammatory disorders were significantly more frequent in the IUO group (37% versus 25%; P = 0.03). 18F-FDG PET imaging had a sensitivity of 93% (89-96%), a specificity of 35% (29-42%), and made a positive contribution to the final diagnosis in 25% (21-29%) of cases. IUO was significantly associated with contributive 18F-FDG PET imaging compared to FUO (aOR 2.21 [95% CI 1.31-3.72]; P = 0.003). Among those with contributive 18F-FDG PET imaging, giant cell arteritis (IUO 25% versus FUO 12%) and polymyalgia rheumatica (IUO 17% versus FUO 1%) were numerically more frequent in the IUO group.
    Conclusion: The diagnostic contribution of 18F-FDG PET was higher among those with IUO, most likely due to differences in diagnostic spectrum.
    MeSH term(s) Humans ; Female ; Middle Aged ; Male ; Fluorodeoxyglucose F18 ; Fever of Unknown Origin/diagnostic imaging ; Fever of Unknown Origin/etiology ; Retrospective Studies ; Positron-Emission Tomography/methods ; Inflammation/diagnostic imaging ; Radiopharmaceuticals
    Chemical Substances Fluorodeoxyglucose F18 (0Z5B2CJX4D) ; Fluorine-18 (GZ5I74KB8G) ; Radiopharmaceuticals
    Language English
    Publishing date 2023-02-02
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 1038679-8
    ISSN 1879-0828 ; 0953-6205
    ISSN (online) 1879-0828
    ISSN 0953-6205
    DOI 10.1016/j.ejim.2023.01.025
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    Zs.A 2608: Show issues Location:
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  10. Article ; Online: Association Between Vascular

    Moreel, Lien / Coudyzer, Walter / Boeckxstaens, Lennert / Betrains, Albrecht / Molenberghs, Geert / Vanderschueren, Steven / Claus, Eveline / Van Laere, Koen / Blockmans, Daniel

    Annals of internal medicine

    2023  Volume 176, Issue 10, Page(s) 1321–1329

    Abstract: Background: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular : Objective: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions.: Design: Prospective ... ...

    Abstract Background: Previous studies have shown that patients with giant cell arteritis (GCA) who have vascular
    Objective: To measure the association between vascular FDG uptake at diagnosis and the change in aortic dimensions.
    Design: Prospective cohort study.
    Setting: University Hospitals Leuven.
    Patients: 106 patients with GCA and FDG positron emission tomography (PET) imaging 3 days or less after initiation of glucocorticoids.
    Measurements: Patients had PET and computed tomography (CT) imaging at diagnosis and CT imaging yearly for a maximum of 10 years. The PET scans were scored 0 to 3 in 7 vascular areas and summed to a total vascular score (TVS). The PET scan results were positive when FDG uptake was grade 2 or greater in any large vessel. The association between vascular FDG uptake and aortic dimensions was estimated by linear mixed-effects models with random intercept and slope.
    Results: When compared with patients with a negative PET scan result, those with a positive scan result had a greater increase in the diameter of the ascending aorta (difference in 5-year progression, 1.58 mm [95% CI, 0.41 to 2.74 mm]), the diameter of the descending aorta (1.32 mm [CI, 0.38 to 2.26 mm]), and the volume of the thoracic aorta (20.5 cm³ [CI, 4.5 to 36.5 cm³]). These thoracic aortic dimensions were also positively associated with TVS. Patients with a positive PET scan result had a higher risk for thoracic aortic aneurysms (adjusted hazard ratio, 10.21 [CI, 1.25 to 83.3]).
    Limitation: The lengthy inclusion and follow-up period resulted in missing data and the use of different PET machines.
    Conclusion: Higher TVS was associated with greater yearly increase in thoracic aortic dimensions. Performing PET imaging at diagnosis may help to estimate the risk for aortic aneurysm formation.
    Primary funding source: None.
    MeSH term(s) Humans ; Fluorodeoxyglucose F18 ; Giant Cell Arteritis/complications ; Giant Cell Arteritis/diagnostic imaging ; Cohort Studies ; Prospective Studies ; Positron-Emission Tomography/methods
    Chemical Substances Fluorodeoxyglucose F18 (0Z5B2CJX4D)
    Language English
    Publishing date 2023-10-03
    Publishing country United States
    Document type Journal Article
    ZDB-ID 336-0
    ISSN 1539-3704 ; 0003-4819
    ISSN (online) 1539-3704
    ISSN 0003-4819
    DOI 10.7326/M23-0679
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