559 results match your criteria: "Wolfson Wohl Cancer Research Centre; Garscube Estate[Affiliation]"

Background: Adherence to post-polypectomy surveillance is poor despite evidence that it is associated with lower risk of future colorectal cancer.

Methods: We evaluated 6,210 bowel screening participants between 2009-2016 in NHS Greater Glasgow and Clyde to assess potential barriers to post-polypectomy surveillance.

Results: Increasing deprivation (Scottish Index of Multiple Deprivation quintile 1 vs 5; OR 1.

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Nanopore sequencing reveals that DNA replication compartmentalisation dictates genome stability and instability in Trypanosoma brucei.

Nat Commun

January 2025

University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, Glasgow, G12 8TA, United Kingdom.

The Trypanosoma brucei genome is structurally complex. Eleven megabase-sized chromosomes each comprise a transcribed core flanked by silent subtelomeres, housing thousands of Variant Surface Glycoprotein (VSG) genes. Additionally, hundreds of sub-megabase chromosomes contain 177 bp repeats of unknown function, and VSG transcription sites localise to many telomeres.

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Purpose: To assess the association between neoadjuvant therapy and overall survival (OS) in patients with left-sided resectable pancreatic cancer (RPC) compared to upfront surgery.

Background: Left-sided pancreatic cancer is associated with worse OS compared to right-sided pancreatic cancer. Although neoadjuvant therapy is currently seen as not effective in patients with RPC, current randomized trials included mostly patients with right-sided RPC.

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IL-7 promotes integrated glucose and amino acid sensing during homeostatic CD4 T cell proliferation.

Cell Rep

January 2025

School of Infection, Inflammation and Immunology, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK. Electronic address:

Interleukin (IL)-7 promotes T cell expansion during lymphopenia. We studied the metabolic basis in CD4 T cells, observing increased glucose usage for nucleotide synthesis and oxidation in the tricarboxylic acid (TCA) cycle. Unlike other TCA metabolites, glucose-derived citrate does not accumulate upon IL-7 exposure, indicating diversion into other processes.

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Mutational signatures define immune and Wnt-associated subtypes of ampullary carcinoma.

Gut

December 2024

Biotech Research and Innovation Center (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

Background And Objective: Ampullary carcinoma (AMPAC) taxonomy is based on morphology and immunohistochemistry. This classification lacks prognostic reliability and unique genetic associations. We applied an approach of integrative genomics characterising patients with AMPAC exploring molecular subtypes that may guide personalised treatments.

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Purpose: Carbonic anhydrase IX (CAIX) is a well-established prognostic marker in breast cancer (BC). Nevertheless, this prognostic value is yet to be confirmed in BC subtypes. This study aims to investigate the prognostic effects of CAIX in oestrogen receptor (ER)-negative (ER-) BCs and to establish pathways related to cytoplasmic CAIX expression in ER- and lymph node-negative BCs.

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HER2 and αβ integrin are independent predictors of breast cancer survival and metastasis. We identify an αβ/HER2 cross-talk mechanism driving invasion, which is dysregulated in drug-resistant HER2+ breast cancer cells. Proteomic analyses reveal ligand-bound αβ recruits HER2 and a trafficking subnetwork, comprising guanosine triphosphatases RAB5 and RAB7A and the Rab regulator guanine nucleotide dissociation inhibitor 2 (GDI2).

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Response of Blood Pressure to Renal Denervation Is Not Associated With Genetic Variants.

Hypertension

January 2025

Department of Internal Medicine III, Cardiology, Angiology, Intensive Care Medicine, Saarland University Hospital, Homburg, Germany (L.L., M.K., M.B., F.M.).

Background: Renal denervation lowers blood pressure (BP) in patients with uncontrolled hypertension. We conducted an unbiased genomic screen to identify genetic variants that may associate with BP response to renal denervation (RDN).

Methods: Patients (n=268) with uncontrolled resistant hypertension (baseline BP, 166±21/90±15 mm Hg) who underwent endovascular RDN using the Symplicity catheter (Medtronic, Inc, Santa Rosa, CA) were included.

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Children diagnosed with acute myeloid leukaemia (paediatric AML [pAML]) have limited treatment options and relapse rates due to chemoresistance and refractory disease are over 30%. Current treatment is cytotoxic and in itself has long-lasting harsh side effects. New, less toxic treatments are needed.

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Various bacteria are suggested to contribute to colorectal cancer (CRC) development, including pks Escherichia coli, which produces the genotoxin colibactin that induces characteristic mutational signatures in host epithelial cells. However, it remains unclear how the highly unstable colibactin molecule is able to access host epithelial cells to cause harm. Here, using the microbiota-dependent ZEB2-transgenic mouse model of invasive CRC, we demonstrate that the oncogenic potential of pks E.

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Pancreatic cancer is characterized by the prevalence of oncogenic mutations in KRAS. Previous studies have reported that altered KRAS gene dosage drives progression and metastasis in pancreatic cancer. Whereas the role of oncogenic KRAS mutations is well characterized, the relevance of the partnering wild-type (WT) KRAS allele in pancreatic cancer is less well understood and controversial.

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Article Synopsis
  • Eftilagimod alpha (efti) is a protein that activates immune cells, potentially overcoming resistance to PD-(L)1 inhibitors, and was tested with pembrolizumab on NSCLC patients who had previously failed anti-PD-(L)1 therapy.
  • In a study of 36 patients, efti was administered alongside pembrolizumab, with primary focus on the objective response rate and secondary measures including overall survival and disease control.
  • Results showed modest activity with an 8.3% objective response rate and a median overall survival of 9.9 months, particularly benefiting patients with higher PD-(L)1 expression, while the treatment was well-tolerated without severe adverse events.
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Objectives: Body composition assessment using CT images at the L3-level is increasingly applied in cancer research and has been shown to be strongly associated with long-term survival. Robust high-throughput automated segmentation is key to assess large patient cohorts and to support implementation of body composition analysis into routine clinical practice. We trained and externally validated a deep learning neural network (DLNN) to automatically segment L3-CT images.

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Article Synopsis
  • Intraductal oncocytic papillary neoplasms (IOPNs) are now identified as distinct from intraductal papillary mucinous neoplasms (IPMNs), with limited information on their recurrence and survival outcomes.
  • A study analyzed outcomes of 415 patients with invasive IOPNs and adenocarcinoma from IPMN over a median of 6 years, finding similar recurrence rates between invasive IOPNs and ductal A-IPMN, but poorer survival compared to colloid A-IPMN.
  • The research concluded that invasive IOPNs behave like aggressive cancers, with adjuvant chemotherapy showing no significant impact on recurrence rates in any of the studied cancer types.
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Background: Transforming growth factor β-activated protein kinase-1 (TAK1) plays an important role in MAPK and NFκB pathways and has been associated with colorectal cancer. The aim of this study was to determine how cytoplasmic and juxtanuclear punctate staining of TAK1 relates to immune checkpoint expression and cancer specific survival in colorectal cancer.

Methods: Protein expression was assessed by immunohistochemistry on tissue microarrays from primary curative colorectal cancer resected specimens.

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Purpose: Eftilagimod alpha (efti), a soluble LAG3 protein, activates antigen-presenting cells (APC) and downstream T cells. TACTI-002 (part C) evaluated whether combining efti with pembrolizumab led to strong antitumor responses in patients with second-line recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) while demonstrating good tolerability.

Patients And Methods: In this multinational phase II trial using Simon's two-stage design, patients who were PD-L(1)-naïve with R/M HNSCC who had failed first-line platinum-based therapy, unselected for PD-L1, received intravenous pembrolizumab (200 mg, once every 2 weeks) combined with subcutaneous efti (30 mg once every 2 weeks for 24 weeks and once every 3 weeks thereafter).

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Introduction: Metabolic reprogramming is a hallmark feature of pancreatic ductal adenocarcinoma (PDAC). A pancreatic juice (PJ) metabolic signature has been reported to be prognostic of oncological outcome for PDAC. Integration of PJ profiling with transcriptomic and spatial characterization of the tumor microenvironment would help in identifying PDACs with peculiar vulnerabilities.

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Bioengineered niches that recreate physiological extracellular matrix organisation to support long-term haematopoietic stem cells.

Nat Commun

July 2024

Centre for the Cellular Microenvironment, School of Molecular Biosciences, The Advanced Research Centre, 11 Chapel Lane, University of Glasgow, Glasgow, G11 6EW, United Kingdom.

Article Synopsis
  • Scientists are working on using special types of stem cells called Long-term reconstituting haematopoietic stem cells (LT-HSCs) to help treat blood problems through transplants.
  • One challenge is that LT-HSCs are hard to find and don’t live long in lab conditions, but researchers have made progress in keeping them alive using special support systems.
  • They created a new game-changing environment using soft materials that help these LT-HSCs survive and even support gene editing, which could improve treatment for blood disorders!
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The NFκB pathway, known as the central regulator of inflammation, has a well-established role in colorectal cancer (CRC) initiation, progression, and therapy resistance. Due to the pathway's overarching roles in CRC, there have been efforts to characterise NFκB family members and target the pathway for therapeutic intervention. Initial research illustrated that the canonical NFκB pathway, driven by central kinase IKKβ, was a promising target for drug intervention.

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Article Synopsis
  • The study examines the outcomes of different precursor epithelial subtypes of adenocarcinoma from intraductal papillary mucinous neoplasms (A-IPMN), focusing on clinical features and recurrence patterns among patients who underwent pancreatic surgery.
  • A total of 297 patients were analyzed, revealing that gastric, pancreatobiliary, and mixed subtypes have similar outcomes that are worse than the intestinal subtype in terms of recurrence and overall survival.
  • The research found that adjuvant chemotherapy specifically improved survival rates in the pancreatobiliary subtype, but not in gastric, intestinal, or mixed subtypes, indicating a potential area for further exploration in treatment strategies.
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Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients' prognosis were invesigated.

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Article Synopsis
  • Steroids play a key role in treating acute lymphoblastic leukaemia (ALL) in young patients, but can lead to serious neuropsychiatric symptoms (SRNS).
  • A study examined 1813 patients from 2000 to 2017, finding that 5.2% experienced significant SRNS, mainly during the early and intensification phases of treatment, with dexamethasone linked to 86% of cases.
  • The most common SRNS symptoms were psychosis, agitation, and aggression, and 87% of those affected received pharmacological treatment, highlighting the need for more awareness and research on managing SRNS in ALL therapy.
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Ferroptosis is a distinct form of necrotic cell death caused by overwhelming lipid peroxidation, and emerging evidence indicates a major contribution to organ damage in multiple pathologies. However, ferroptosis has not yet been visualized in vivo due to a lack of specific probes, which has severely limited the study of how the immune system interacts with ferroptotic cells and how this process contributes to inflammation. Consequently, whether ferroptosis has a physiological role has remained a key outstanding question.

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Article Synopsis
  • - The study investigates factors affecting long-term survival and recurrence in patients with adenocarcinoma from intraductal papillary mucinous neoplasms, focusing on those who had pancreatic resection between 2010 and 2017 in Europe and Asia.
  • - It analyzed data from 288 patients, revealing that 48% experienced recurrence within about 98 months, with 35% remaining disease-free at the 5-year mark.
  • - Key negative predictors for long-term disease-free survival included multivisceral resection, tumor location in the pancreatic tail, poor differentiation, lymphovascular invasion, and perineural invasion, leading to the development of a predictive model with a good success rate.
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