Publications by authors named "Smyth E"

Article Synopsis
  • - The ESMO Clinical Practice Guidelines for oncogene-addicted metastatic non-small-cell lung cancer (mNSCLC) were updated into Pan-Asian adapted (PAGA) guidelines to better address the needs of Asian patients.
  • - A panel of experts from multiple Asian oncological societies collaborated to create these guidelines, focusing on scientific evidence rather than local treatment practices or drug availability.
  • - The guidelines aim to standardize the management of oncogene-addicted mNSCLC across Asia, while acknowledging regional differences in screening, treatment resources, and drug reimbursement policies.
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Mantle cell lymphoma (MCL) is a clinically heterogeneous B-cell neoplasm with unique clinicopathological features, accounting for 5% of all non-Hodgkin lymphoma. Although for many chemoimmunotherapy can lead to durable remissions, those with poor baseline prognostic factors, namely blastoid morphology, TP53 aberrancy and Ki67 >30%, will have less durable responses to conventional therapies. With this in mind, clinical trials have focused on novel targeted therapies to improve outcomes.

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Background: Patients with gastro-oesophageal adenocarcinoma with tumour-positive lymph nodes (ypN+) or positive surgical margins (R1) following neoadjuvant chemotherapy and resection are at high risk of recurrence. Adjuvant nivolumab is effective in oesophageal/oesophagogastric junction cancer and residual pathological disease following chemoradiation and surgery. Immune checkpoint inhibition has shown efficacy in advanced gastro-oesophageal cancer.

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Background: High expression of programmed death-ligand 1 (PD-L1) has been recognized as a marker of improved efficacy of immunotherapy in gastroesophageal adenocarcinoma (GEA); however, the optimal PD-L1 cut-off is still debated. The aim of the present review was to analyze available phase III trials and to identify the appropriate PD-L1 expression cut-off for GEA.

Methods: Phase III trials investigating the efficacy of anti-programmed cell death protein 1 (PD-1) therapies in addition to standard chemotherapy versus standard chemotherapy in the first-line setting were selected.

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Background: Rapid antigen tests (RATs) are suitable for point-of-care testing, require no laboratory time, and give immediate results. However, are RATs useful for detecting asymptomatic COVID-19 infection when compared with polymerase chain reaction (PCR) testing in health care settings?

Methods: RAT testing was carried out on all new admissions without a history of confirmed COVID-19 infection within 3 months of admission. PCR testing was carried out on all patients with a positive RAT for confirmation purposes.

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Article Synopsis
  • Testicular germ cell tumours (TGCT) are the most common cancers found in young men, including seminoma and non-seminoma types.
  • This study uses whole genome sequencing to analyze adult TGCTs, providing a detailed genomic profile that includes mutations, structural variations, and DNA amplifications.
  • The research uncovers correlations between genetic changes and the different growth patterns of TGCT subtypes, highlighting late genomic duplication in some cases and a common immune disruption mechanism in seminomas.
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Background: Older people with HIV (PWH) are at risk of polypharmacy (taking multiple medications). Most medications may be necessary and indicated to manage HIV (e.g.

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Background: While the benefit of immune checkpoint inhibitors (ICI) is well established in programmed death-ligand 1 high (PD-L1) advanced gastroesophageal adenocarcinoma (GEAC), there remains significant controversy about their benefit in PD-L1 GEAC. To elucidate the benefit of ICI in PD-L1 and PD-L1 GEAC, we conducted an analysis leveraging individual patient data (IPD) extracted from Kaplan-Meier (KM) plots of pivotal trials.

Methods: KM curves from randomized clinical trials investigating the efficacy of ICI for advanced GEAC were extracted from published articles.

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  • Tumor cell-derived prostaglandin E2 (PGE2) promotes immunosuppression in the tumor microenvironment by influencing immune cells, but its specific role in tumor cells remains unexplored.
  • Deleting the PGE2 synthesis enzyme or blocking its receptor (EP4) in pancreatic cancer cells activates T cells, changes the immune environment, and inhibits tumor growth.
  • Combining EP4 receptor blockade with immunotherapy leads to complete tumor regressions and enhances immune memory, highlighting the importance of targeting the PGE2 signaling pathway for potential cancer treatments.
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α-l-(3'-2')-Threofuranosyl nucleic acid (TNA) pairs with itself, cross-pairs with DNA and RNA, and shows promise as a tool in synthetic genetics, diagnostics, and oligonucleotide therapeutics. We studied primer insertion and extension reactions catalyzed by human trans-lesion synthesis (TLS) DNA polymerase η (hPol η) opposite a TNA-modified template strand without and in combination with -alkyl thymine lesions. Across TNA-T (tT), hPol η inserted mostly dAMP and dGMP, dTMP and dCMP with lower efficiencies, followed by extension of the primer to a full-length product.

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Despite our increased understanding of the biological and molecular aspects of gastro-oesophageal tumourigenesis, the identification of prognostic or predictive factors remains challenging. Patients with resectable gastric and oesophageal adenocarcinoma are often treated similarly after surgical resection, regardless of their tumour biology, clinical characteristics, and histological treatment response. Substantial progress has been made in the past 5 years in managing patients with gastric or oesophageal adenocarcinoma, including the use of immune checkpoint inhibitors and new targeted therapies, leading to substantial improvements in clinical outcomes.

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Aims: Oesophago-gastric cancers (OGCs) are amongst the most commonly diagnosed malignancies worldwide and are associated with high disease-related mortality. Predictive biomarkers are molecules that can be objectively measured and used to indicate a likely response to therapeutic intervention, thus facilitating individualised cancer therapy. However, there remains variation in uptake and implementation of biomarker testing across the UK.

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Gastroesophageal (GE) and pancreatobiliary (PB) cancers represent a significant clinical challenge. In this context, it is critical to understand the key molecular targets within these malignancies including how they are assayed for as well as the clinical actionability of these targets. Integrating biomarkers into the standard of care presents a critical avenue for refining treatment paradigms.

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Purpose: Exercise prehabilitation aims to increase preoperative fitness, reduce post-operative complications, and improve health-related quality of life. For prehabilitation to work, access to an effective programme which is acceptable to stakeholders is vital. The aim was to explore acceptability of exercise prehabilitation before cancer surgery among key stakeholders specifically patients, family members and healthcare providers.

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  • Tobacco use alters the oral microbiome, affecting the diversity and abundance of bacterial communities in smokers and smokeless tobacco users compared to non-users over a 4-month period.
  • Cigarette and smokeless tobacco users showed a higher diversity of bacteria, with more Firmicutes and fewer Proteobacteria, while non-users had more beneficial genera like Actinomyces and Neisseria.
  • Some bacterial species shifted significantly over time, and opportunistic pathogens were identified in tobacco users, providing new insights into the oral health impacts of different tobacco products.
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Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD).

Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer.

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Article Synopsis
  • Surgery combined with chemotherapy is the standard treatment for locally advanced gastric cancer (GC) and gastroesophageal junction cancer (GEJC), but outcomes are often poor, especially in specific genetic subtypes like dMMR/MSI-high.* -
  • Analysis from several clinical trials shows that patients with MSI-high tumors generally have better survival rates than those with MSS/MSI-low tumors, and that female patients with MSS/MSI-low tumors tend to live longer than their male counterparts.* -
  • The study emphasizes that sex can influence the effectiveness of treatments for both MSI-high and MSS/MSI-low non-metastatic GC/GEJC, with surprisingly higher chemotherapy risks noted in females with MSI-high cancers.*
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  • Most oesophagogastric adenocarcinomas (OGAs) and colorectal cancers (CRCs) are mismatch repair proficient, which means they typically don't respond well to immune checkpoint therapies; this study looks at combining domatinostat, a histone deacetylase inhibitor, with avelumab, an anti-PD-L1 antibody, in treating these cancers.
  • The clinical trial involved a multicenter phase II study where patients received different doses of domatinostat alongside avelumab to find the best dosage and assess the treatment's effectiveness over six months.
  • Results showed that in the OGA group, about 22.2% had a positive response to the treatment with a median disease control duration of 11
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The European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of patients with gastric cancer (GC), published in late 2022 and the updated ESMO Gastric Cancer Living Guideline published in July 2023, were adapted in August 2023, according to previously established standard methodology, to produce the Pan-Asian adapted (PAGA) ESMO consensus guidelines for the management of Asian patients with GC. The adapted guidelines presented in this manuscript represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with GC representing the oncological societies of China (CSCO), Indonesia (ISHMO), India (ISMPO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO), coordinated by ESMO and the Japanese Society of Medical Oncology (JSMO). The voting was based on scientific evidence and was independent of the current treatment practices, drug access restrictions and reimbursement decisions in the different Asian regions represented by the 10 oncological societies.

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The growth of graphene on silicon carbide on silicon offers a very attractive route towards novel wafer-scale photonic and electronic devices that are easy to fabricate and can be integrated in silicon manufacturing. Using a Ni/Cu catalyst for the epitaxial growth of graphene has been successful in the mitigation of the very defective nature of the underlying silicon carbide on silicon, leading to a consistent graphene coverage over large scales. A more detailed understanding of this growth mechanism is warranted in order to further optimise the catalyst composition, preferably the use of characterization measurements.

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