Publications by authors named "Stephen Jacques Hamilton-Dutoit"

Article Synopsis
  • Advances in treating classic Hodgkin lymphoma (cHL) have led to an 80% overall survival rate, but survivors face risks of long-term complications like cardiac and pulmonary issues.
  • Research using advanced protein analysis compared samples from cHL patients with and without bleomycin-induced pulmonary toxicity (BPT), revealing distinct protein expression and disrupted pathways linked to BPT risk.
  • Key proteins like JAK3, BID, and MMP9 were found at different levels in patients with BPT, indicating that certain protein profiles in biopsies might predict poorer survival outcomes in these individuals.
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Follicular lymphoma (FL) is characterized by an indolent nature and generally favorable prognosis, yet poses a particular clinical challenge, since disease progression is observed in a notable subset of patients. Currently, it is not possible to anticipate which patients will be at risk of progression, highlighting the need for reliable predictive biomarkers that can be detected early in the disease. We applied tandem-mass-tag labelled nano-liquid chromatography tandem mass spectrometry (nLC-MS/MS) on 48 diagnostic formalin-fixed, paraffin-embedded tumor samples from patients with advanced-stage FL.

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Classic Hodgkin lymphoma (CHL) is a highly curable disease, even in advanced stages. Controversy remains over whether bone involvement negatively affects overall and progression-free survival in patients treated with intensive chemotherapy regimens. Whether cases that present with bone lesions harbor specific tumor microenvironmental features is unknown.

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Follicular lymphoma (FL) is an indolent lymphoma with a generally favorable prognosis. However, histological transformation (HT) to a more aggressive disease leads to markedly inferior outcomes. This study aims to identify biological differences predictive of HT at the time of initial FL diagnosis.

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Post-transplant lymphoproliferative disorders (PTLD) are iatrogenic immune deficiency-associated lymphoid/plasmacytic proliferations developing due to immunosuppression in solid organ or hematopoietic stem cell allograft patients. PTLD are characterized by abnormal proliferation of lymphoid cells and have a heterogeneous clinical behavior. We profiled expression of >700 tumor microenvironment (TME)-related genes in 75 post-transplant aggressive B-cell lymphomas (PTABCL).

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Article Synopsis
  • Follicular lymphoma (FL) is a slow-growing cancer that can sometimes become more aggressive, leading to higher mortality risks for patients, especially due to early progression or histological transformation (HT).
  • The study investigated the expression levels of an immunoinhibitory molecule called indoleamine 2,3-dioxygenase 1 (IDO1) in tissue samples from FL patients, comparing those whose disease remained stable and those who experienced transformation.
  • Although no significant differences in IDO1 levels were found between the groups, high expression was noted in all samples, suggesting that IDO1 may be targeted in future therapies, especially as it correlates with another immune checkpoint, PD-1.
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  • Inflammation and metabolic dysfunction are key factors in non-alcoholic fatty liver disease (NAFLD), which is rapidly increasing globally.
  • Researchers studied 142 NAFLD patients to explore the genetic link between specific IFNL4 variants and fibrosis, finding a higher frequency of a non-functional IFNL4 allele in patients with significant fibrosis.
  • Contrary to expectations, experiments in an animal model revealed that interferon treatment led to increased liver fibrosis, highlighting a complex relationship between IFN and fibrosis development.
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Myeloproliferative neoplasia (MPN) and lymphoma are regarded as distinct diseases with different pathogeneses. However, patients that are diagnosed with both malignancies occur more frequently in the population than expected. This has led to the hypothesis that the two malignancies may, in some cases, be pathogenetically related.

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Breast implant-associated anaplastic large cell lymphoma is an uncommon malignancy associated with textured breast implants, and since 2014 13 Danish cases have been identified. Early diagnosis is important to minimise morbidity. Most patients present with swelling of the breast due to seroma within the fibrous capsule, fewer with a tumour.

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Background And Aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.

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Purpose: Follicular lymphoma (FL) is an indolent, yet generally incurable neoplasia with a median survival exceeding 10 years. However, a subset of FL patients experiences histological transformation (HT) to a more aggressive lymphoma, in the majority of cases to diffuse large B-cell lymphoma (DLBCL). This affects both the clinical course and the prognostic outcome, resulting in a markedly reduced survival after transformation.

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Myeloid and lymphoid malignancies are postulated to have distinct pathogenetic mechanisms. The recent observation that patients with a myeloproliferative neoplasm have an increased risk of developing lymphoproliferative malignancy has challenged this assumption. We collected a nationwide cohort of patients with both malignancies.

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Article Synopsis
  • Normal liver tissue is sensitive to radiation, posing challenges in treating liver tumors with radiotherapy.
  • A study using Göttingen minipigs assessed the effects of a single, high dose of radiation on liver functions and regeneration, comparing irradiated pigs to controls.
  • Results showed increased bile acid secretion and hepatocellular regeneration in irradiated pigs, suggesting that this model could help improve understanding of radiation-induced liver injury and inform protective strategies.
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  • Galectin-1 (Gal-1) is linked to poor prognosis in various cancers, including some types of lymphoma with CD30 expression, but its role in peripheral T-cell lymphomas (PTCL) had not been thoroughly studied.
  • A study analyzed Gal-1 expression in 169 PTCL specimens, finding that while overall survival (OS) wasn't significantly affected by Gal-1 levels in the entire cohort, patients with high Gal-1 in the CD30-positive group had a much worse 5-year OS compared to those with low Gal-1.
  • High Gal-1 expression was also associated with fewer cytotoxic T cells in the tumor microenvironment and consistently predicted worse outcomes in both univariate and multivariate analyses.
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Aims: Metformin is first-line treatment of type 2 diabetes mellitus and reduces cardiovascular events in patients with insulin resistance and type 2 diabetes. Target tissue for metformin action is thought to be the liver, where metformin distribution depends on facilitated transport by polyspecific transmembrane organic cation transporters (OCTs). Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in the western world with strong associations to insulin resistance and the metabolic syndrome, but whether NAFLD affects metformin biodistribution to the liver is not known.

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The literature is inconsistent as to how coffee affects metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. This study aimed to evaluate the effects of unfiltered coffee on diet-induced MetS and investigate whether or not phenolic acids and trigonelline are the main bioactive compounds in coffee. Twenty-four male Sprague‒Dawley rats were fed a high-fat (35% W/W) diet plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5--caffeoylquinic acid, caffeic acid, and trigonelline).

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Peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) constitutes a heterogeneous category of lymphomas, which do not fit into any of the specifically defined T-cell lymphoma entities. Both the pathogenesis and tumor biology in PTCL-NOS are poorly understood. Protein expression in pretherapeutic PTCL-NOS tumors was analyzed by proteomics.

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Anaplastic large cell lymphomas (ALCLs) are CD30-positive T-cell non-Hodgkin lymphomas broadly segregated into ALK-positive and ALK-negative types. Although ALK-positive ALCLs consistently bear rearrangements of the tyrosine kinase gene, ALK-negative ALCLs are clinically and genetically heterogeneous. About 30% of ALK-negative ALCLs have rearrangements of and have excellent long-term outcomes with standard therapy.

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Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study.

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Despite better therapeutic options and improved survival of diffuse large B-cell lymphoma (DLBCL), 30-40% of the patients experience relapse or have primary refractory disease with a dismal prognosis. To identify biological correlates for treatment resistance, we profiled microRNAs (miRNAs) of matched primary and relapsed DLBCL by next-generation sequencing. Altogether 492 miRNAs were expressed in the DLBCL samples.

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Objective: It has been hypothesized that Lewy pathology initiates in the enteric nervous system years prior to debut of clinical motor symptoms in Parkinson disease patients. This study investigates whether Lewy pathology is present in various gastrointestinal tract tissues from Parkinson disease patients in the prodromal phase.

Methods: We used the Danish National Pathology Registry to identify archived paraffin-embedded tissue blocks from 57 Parkinson disease patients (98 blocks) and 90 control subjects (98 blocks).

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We describe the application of proteomic techniques for protein profiling and biomarker discovery in malignant lymphoma. Hematologic malignancies are primarily characterized by their clinical, morphological, immunophenotypical, and molecular-genetic features. However, when based on these parameters, apparently identical lymphomas may show distinct clinical courses, suggesting underlying biological heterogeneity.

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