Publications by authors named "Helen L Reeves"

Background & Aims: The combination of atezolizumab and bevacizumab (atezo+bev) is the current standard of care for advanced hepatocellular carcinoma (HCC), providing a median overall survival (OS) of 19.2 months. Here, we aim to uncover the underlying cellular processes driving clinical benefit versus resistance to atezo+bev.

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Article Synopsis
  • Drug-induced liver injury (DILI), particularly from acetaminophen (APAP) overdose, is a major factor in acute liver failure and liver transplants in the Western world.
  • Research shows that neddylation, a modification important for mitochondrial function, is increased in liver samples from APAP injury patients and mice with APAP overdose.
  • The inhibitor MLN4924 reduces liver cell damage and enhances regeneration in APAP injury, and the study identifies crucial elements in this process, suggesting new avenues for targeted DILI treatments.
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Objectives: The study aimed to assess the feasibility, acceptability and safety of delivering a home-based telehealth exercise intervention to older patients with hepatocellular carcinoma (HCC).

Design: Non-randomised feasibility study.

Setting: Patients were recruited from UK outpatient liver cancer clinics.

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Article Synopsis
  • - The study investigates the relationship between clonal hematopoiesis of indeterminate potential (CHIP) and the development of hepatocellular carcinoma (HCC) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD).
  • - A sample of 208 individuals with MASLD-HCC and controls was analyzed through whole exome sequencing, revealing that CHIP occurred in 13.1% of participants, with significant correlations to age and advanced liver fibrosis.
  • - Findings indicate that certain CHIP-related genetic mutations (particularly non-DNTM3A and TET2) are independently linked to HCC progression, suggesting that CHIP could be an important factor in identifying patients at risk for liver cancer.
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Introduction: The COVID-19 pandemic has caused severe disruption of healthcare services worldwide and interrupted patients' access to essential services. During the first lockdown, many healthcare services were shut to all but emergencies. In this study, we aimed to determine the immediate and long-term indirect impact of COVID-19 health services utilisation on hepatocellular cancer (HCC) outcomes.

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Hepatocellular carcinoma (HCC), the most common type of liver cancer, has very poor outcomes. Current therapies often have low efficacy and significant toxicities. Thus, there is a critical need for the development of novel therapeutic approaches for HCC.

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Objectives: The Glucokinase Regulatory Protein GKRP, encoded by GCKR, enables acute regulation of liver glucokinase to support metabolic demand. The common human GCKR rs1260326:Pro446 > Leu variant within a large linkage disequilibrium region associates with pleiotropic traits including lower Type 2 diabetes risk and raised blood triglycerides and cholesterol. Whether the GCKR-P446 > L substitution is causal to the raised lipids is unknown.

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Introduction: The burden of metabolic (dysfunction) associated fatty liver disease (MAFLD) is rising mirrored by an increase in hepatocellular cancer (HCC). MAFLD and its sequelae are characterized by perturbations in lipid handling, inflammation, and mitochondrial damage. The profile of circulating lipid and small molecule metabolites with the development of HCC is poorly characterized in MAFLD and could be used in future studies as a biomarker for HCC.

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Introduction: Heparin sulphate proteoglycans in the liver tumour microenvironment (TME) are key regulators of cell signalling, modulated by sulfatase-2 (SULF2). SULF2 overexpression occurs in hepatocellular carcinoma (HCC). Our aims were to define the nature and impact of SULF2 in the HCC TME.

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Objective: Hepatocellular carcinoma (HCC) deaths are rising alarmingly. Many patients are unsuitable for available therapies. Poor response rates further hamper outcomes for those that are.

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Acetaminophen overdose is one of the leading causes of acute liver failure and liver transplantation in the Western world. Magnesium is essential in several cellular processess. The Cyclin M family is involved in magnesium transport across cell membranes.

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Background And Aims: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. The NF-κB transcription factor family subunit c-Rel is typically protumorigenic; however, it has recently been reported as a tumor suppressor. Here, we investigated the role of c-Rel in HCC.

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Background: The number of incident cases and deaths from primary liver cancer, predominantly hepatocellular carcinoma (HCC), has increased markedly in the last two decades. HCC is generally diagnosed at an advanced stage, and most new cases are in people aged over 70 years with age-related comorbidities. Treatment options are often limited, with most patients receiving palliative treatment or supportive care only.

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Background & Aims: Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population.

Methods: Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020.

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Hepatocellular carcinoma (HCC) remains one of the most prevalent and deadliest cancers. The poor outcome associated with HCC is dramatically changing due to the advent of effective systemic therapies. Here we discuss the molecular pathogenesis of HCC, molecular classes and determinants of heterogeneity.

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Objective: Hepatocellular carcinoma (HCC) is increasingly associated with non-alcoholic steatohepatitis (NASH). HCC immunotherapy offers great promise; however, recent data suggests NASH-HCC may be less sensitive to conventional immune checkpoint inhibition (ICI). We hypothesised that targeting neutrophils using a CXCR2 small molecule inhibitor may sensitise NASH-HCC to ICI therapy.

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Background: Northern England has been experiencing a persistent rise in the number of primary liver cancers, largely driven by an increasing incidence of hepatocellular carcinoma (HCC) secondary to alcohol-related liver disease and non-alcoholic fatty liver disease. Here we review the effect of the COVID-19 pandemic on primary liver cancer services and patients in our region.

Objective: To assess the impact of the COVID-19 pandemic on patients with newly diagnosed liver cancer in our region.

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Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.

Methods: We performed whole-exome sequencing in individuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs.

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Article Synopsis
  • Acetaminophen (APAP) can cause severe liver damage by triggering endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) in liver cells, but the detailed mechanisms behind this are not well understood.
  • In studies using specific mice models, it was found that the activation of UPR and the JNK1/2 pathway were significant in APAP-induced liver toxicity, and that the XBP1 gene played a crucial role in this process.
  • Blocking or reducing the activity of XBP1 in liver cells helped reduce liver injury by promoting autophagy and lowering the expression of CYP2E1, indicating potential new treatments for serious liver damage.
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The success of atezolizumab plus bevacizumab treatment contributed to a shift in systemic therapies for hepatocellular carcinoma (HCC) towards combinations that include cancer immunotherapeutic agents. Thus far, the principal focus of cancer immunotherapy has been on interrupting immune checkpoints that suppress antitumour lymphocytes. As well as lymphocytes, the HCC environment includes numerous other immune cell types, among which neutrophils are emerging as an important contributor to the pathogenesis of HCC.

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The prevalence of obesity and non-alcoholic fatty liver disease (NAFLD) associated hepatocellular carcinoma (HCC) is rising, even in the absence of cirrhosis. We aimed to develop a murine model that would facilitate further understanding of NAFLD-HCC pathogenesis. A total of 144 C3H/He mice were fed either control or American lifestyle (ALIOS) diet, with or without interventions, for up to 48 weeks of age.

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Dysregulation of miRNAs is a hallmark of cancer, modulating oncogenes, tumor suppressors, and drug responsiveness. The multi-kinase inhibitor sorafenib is one of the first-line drugs for advanced hepatocellular carcinoma (HCC), although the outcome for treated patients is heterogeneous. The identification of predictive biomarkers and targets of sorafenib efficacy are sorely needed.

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