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A phase I clinical trial of intrahepatic artery delivery of TG6002 in combination with oral 5-fluorocytosine in patients with liver-dominant metastatic colorectal cancer.
Clin Cancer Res
January 2025
University of Leeds, Leeds, United Kingdom.
Background: Effective treatment for patients with metastatic cancer is limited, particularly for colorectal cancer patients with metastatic liver lesions (mCRC), where accessibility to numerous tumours is essential for favourable clinical outcomes. Oncolytic viruses (OVs) selectively replicate in cancer cells; however, direct targeting of inaccessible lesions is limited when using conventional intravenous or intratumoural administration routes.
Methods: We conducted a multi-centre, dose-escalation, phase I study of vaccinia virus, TG6002, via intrahepatic artery (IHA) delivery in combination with the oral pro-drug 5-fluorocytosine to fifteen mCRC patients.
Public Health.
Alzheimers Dement
December 2024
Harvard T. H. Chan School of Public Health, Boston, MA, USA.
Background: Previous studies yielded inconsistent results regarding the association between red meat intake and cognitive health. We aimed to prospectively examine the associations between processed and unprocessed red meat intakes and various cognitive outcomes.
Method: We assessed diet intake every 2-4 years using food-frequency questionnaires and ascertained incident dementia cases through self-report and death records in 87,424 participants free from Parkinson's disease or baseline dementia, stroke, cancer from the Nurses' Health Study (NHS).
Biomarkers.
Alzheimers Dement
December 2024
UK Dementia Research Institute Centre for Care Research and Technology, London, UK.
Background: The hippocampus is a key site of atrophy in Alzheimer's disease (AD) and MRI derived estimates of hippocampal volume have been shown to be a robust biomarker of AD-related neurodegeneration. However, its application at the individual level is limited by the lack of reference standards from large normative datasets that can be applied across a wide range of settings. We aimed to investigate the utility of hippocampal volume centile scores adjusted for age, sex and total intracranial volume (TIV) derived from a normative data from 101,457 participants across the life course, as a biomarker of neurodegeneration in AD.
View Article and Find Full Text PDFTracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.
Cancer Discov
January 2025
Cancer Dynamics Laboratory, The Francis Crick Institute, London, United Kingdom.
Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.
View Article and Find Full Text PDFLife after Pelvic Exenteration for Rectal Cancer: The Patient and Carer Perspective on Long Term Consequences and Survivorship.
Ann Surg
January 2025
Surgical Outcomes Research Centre (SOuRCe), Royal Prince Alfred Hospital, Sydney, Australia.
Objective: To explore the perspectives and experiences of patients and carers living with the long-term consequences of pelvic exenteration.
Summary Background Data: Pelvic exenteration is accepted as the standard of care for selected patients with locally advanced or recurrent rectal cancer. With contemporary 5-year survival reported at 40-60%, the number of long-term survivors is expected to increase.
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