British Journal of Cancer

BACKGROUND: The associations of vitamin C intake with colorectal cancer (CRC) survival according to tumour KRAS or BRAF mutation status remain unclear. METHODS: We used the inverse probability weighted multivariable Cox proportional hazards regression model to calculate the hazard ratio (HR) of mortality, and spline analysis to evaluate the dose-response relationship in the Nurses' Health Study and Health Professionals Follow-up Study. We also assessed SLC2A1 mRNA expression according to KRAS or BRAF mutation in the TCGA database...

BACKGROUND: To investigate the predictive ability of high-throughput MRI with deep survival networks for biochemical recurrence (BCR) of prostate cancer (PCa) after prostatectomy. METHODS: Clinical-MRI and histopathologic data of 579 (train/test, 463/116) PCa patients were retrospectively collected. The deep survival network (iBCR-Net) is based on stepwise processing operations, which first built an MRI radiomics signature (RadS) for BCR, and predicted the T3 stage and lymph node metastasis (LN+) of tumour using two predefined AI models...

BACKGROUND: Oral epithelial dysplasia (OED) is the precursor to oral squamous cell carcinoma which is amongst the top ten cancers worldwide. Prognostic significance of conventional histological features in OED is not well established. Many additional histological abnormalities are seen in OED, but are insufficiently investigated, and have not been correlated to clinical outcomes. METHODS: A digital quantitative analysis of epithelial cellularity, nuclear geometry, cytoplasm staining intensity and epithelial architecture/thickness is conducted on 75 OED whole-slide images (252 regions of interest) with feature-specific comparisons between grades and against non-dysplastic/control cases...

In recent years, liquid biopsy has emerged as an alternative method to diagnose and monitor tumors. Compared to classical tissue biopsy procedures, liquid biopsy facilitates the repetitive collection of diverse cellular and acellular analytes from various biofluids in a non/minimally invasive manner. This strategy is of greater significance for high-grade brain malignancies such as glioblastoma as the quantity and accessibility of tumors are limited, and there are collateral risks of compromised life quality coupled with surgical interventions...

BACKGROUND: Available data on Mismatch Repair system (MMR) deficiency are conflicting and derived from small studies. Our study aimed to evaluate the therapeutic implications of MMR status in patients with locally advanced rectal cancer (LARC). METHODS: We retrospectively collected data from 318 patients affected by LARC treated in Italy at the Medical Oncology Units of the University Hospital of Cagliari, Istituto Nazionale dei Tumori Milan, and AOU Ospedali Riuniti Ancona...

BACKGROUND: Multiple drug treatments are approved for invasive breast cancer (IBC). We investigated uptake of NICE-recommended oncological drugs and variation by age, comorbidity burden and geographical region. METHODS: Women (aged 50+ years) diagnosed with IBC from 2014 to 2019, were identified from England Cancer Registry data and drug utilisation from Systemic Anti-Cancer Therapy data. Interrupted time series analysis assessed national-level changes in drug use after publication of NICE recommendations...

BACKGROUND: Individual and tumour factors only explain part of observed inequalities in colorectal cancer survival in England. This study aims to investigate inequalities in treatment in patients with colorectal cancer. METHODS: All patients diagnosed with colorectal cancer in England between 2012 and 2016 were followed up from the date of diagnosis (state 1), to treatment (state 2), death (state 3) or censored at 1 year after the diagnosis. A multistate approach with flexible parametric model was used to investigate the effect of income deprivation on the probability of remaining alive and treated in colorectal cancer...

BACKGROUND: Androgen signalling remains the seminal therapeutic approach for the management of advanced prostate cancer. However, most tumours eventually shift towards an aggressive phenotype, characterised by androgen independence and treatment resistance. The cyclic adenosine monophosphate (cAMP) pathway plays a crucial role in regulating various cellular processes, with the phosphodiesterase PDE4D7 being a vital modulator of cAMP signalling in prostate cancer cells. METHODS: Using shRNA-mediated PDE4D7 knockdown in LNCaP cells and downstream analysis via RNA sequencing and phenotypic assays, we replicate clinical observations that diminished PDE4D7 expression promotes an aggressive prostate cancer phenotype...

BACKGROUND: Increasing data indicate that HER2-positive (HER2 + ) breast cancer (BC) subtypes exhibit differential responses to targeted anti-HER2 therapy. This study aims to investigate these differences and the potential underlying molecular mechanisms. METHODS: A large cohort of BC patients (n = 7390) was utilised. The clinicopathological characteristics and differential gene expression (DGE) of HER2+ immunohistochemical (IHC) subtypes, specifically HER2 IHC 3+ and IHC 2 + /Amplified, were assessed and correlated with pathological complete response (pCR) and survival in the neoadjuvant and adjuvant settings, respectively...

The combination of immune checkpoint inhibitors and anti-angiogenic agents is a promising new approach in cancer treatment. Immune checkpoint inhibitors block the signals that help cancer cells evade the immune system, while anti-angiogenic agents target the blood vessels that supply the tumour with nutrients and oxygen, limiting its growth. Importantly, this combination triggers synergistic effects based on molecular and cellular mechanisms, leading to better response rates and longer progression-free survival than treatment alone...

BACKGROUND: Circulating tumour cells (CTCs) are a potential cancer biomarker, but current methods of CTC analysis at single-cell resolution are limited. Here, we describe high-dimensional single-cell mass cytometry proteomic analysis of CTCs in HNSCC. METHODS: Parsortix microfluidic-enriched CTCs from 14 treatment-naïve HNSCC patients were analysed by mass cytometry analysis using 41 antibodies. Immune cell lineage, epithelial-mesenchymal transition (EMT), stemness, proliferation and immune checkpoint expression was assessed alongside phosphorylation status of multiple signalling proteins...

BACKGROUND: We assessed nofazinlimab, an anti-PD-1 antibody, in solid tumors and combined with regorafenib in metastatic colorectal cancer (mCRC). METHODS: This phase 1 study comprised nofazinlimab dose escalation (phase 1a) and expansion (phase 1b), and regorafenib dose escalation (80 or 120 mg QD, days 1-21 of 28-day cycles) combined with 300-mg nofazinlimab Q4W (part 2a) to determine safety, efficacy, and RP2D. RESULTS: In phase 1a (N = 21), no dose-limiting toxicity occurred from 1 to 10 mg/kg Q3W, with 200 mg Q3W determined as the monotherapy RP2D...

BACKGROUND: Delta-like ligand 3 (DLL3) is a therapeutic target in small-cell lung cancer (SCLC). However, how DLL3 expression status affects the tumor microenvironment (TME) and clinical outcomes in SCLC remains unclear. METHODS: This retrospective study included patients with postoperative limited-stage (LS)-SCLC and extensive-stage (ES)-SCLC treated with platinum and etoposide (PE) plus anti-programmed cell death ligand 1 (PD-L1) antibody. We investigated the relationship of DLL3 expression with TME, mutation status, tumor neoantigens, and immunochemotherapy...

BACKGROUND: NME1 has been exploited as a potential translational target for decades. Substantial efforts have been made to upregulate the expression of NME1 and restore its anti-metastasis function in metastatic cancer. METHODS: Cycloheximide (CHX) chase assay was used to measure the steady-state protein stability of NME1 and HSP90α. The NME1-associating proteins were identified by immunoprecipitation combined with mass spectrometric analysis. Gene knockdown and overexpression were employed to examine the impact of HSP90AA1 on intracellular NME1 degradation...

The advent of multi-cancer early detection (MCED) tests has the potential to revolutionise the diagnosis of cancer, improving patient outcomes through early diagnosis and increased use of curative therapies. The ongoing NHS-Galleri trial is evaluating an MCED test developed by GRAIL, and is using as its primary endpoint the absolute incidence of late-stage cancer. Proponents of this outcome argue that if the test reduces the number of patients with advanced, incurable cancer, it can be reasonably assumed to be benefitting patients by reducing cancer mortality...

BACKGROUND: We investigated the application of years of life lost (YLL) in routine cancer statistics using cancer mortality data from 1988 to 2017. METHODS: Cancer mortality data for 17 cancers and all cancers in the UK from 1988 to 2017 were provided by the UK Association of Cancer Registries by sex, 5-year age group, and year. YLL, age-standardised YLL rate (ASYR) and age-standardised mortality rate (ASMR) were estimated. RESULTS: The annual average YLL due to cancer, in the time periods 1988-1992 and 2013-2017, were about 2...

BACKGROUND: Germ cell tumors (GCT) might undergo transformation into a somatic-type malignancy (STM), resulting in a cell fate switch to tumors usually found in somatic tissues, such as rhabdomyosarcomas or adenocarcinomas. STM is associated with a poor prognosis, but the molecular and epigenetic mechanisms triggering STM are still enigmatic, the tissue-of-origin is under debate and biomarkers are lacking. METHODS: To address these questions, we characterized a unique cohort of STM tissues on mutational, epigenetic and protein level using modern and high-throughput methods like TSO assays, 850k DNA methylation arrays and mass spectrometry...

BACKGROUND: Paediatric precision oncology aims to match therapeutic agents to driver gene targets. We investigated whether parents and patients regret participation in precision medicine trials, particularly when their hopes are unfulfilled. METHODS: Parents and adolescent patients completed questionnaires at trial enrolment (T0) and after receiving results (T1). Parents opted-in to an interview at T1. Bereaved parents completed a questionnaire 6-months post-bereavement (T1B)...

BACKGROUND: Neuroblastoma is a paediatric cancer that is characterised by poor prognosis for chemoresistant disease, highlighting the need for better treatment options. Here, we asked whether BH3-mimetics inhibiting BCL2 proteins may eliminate chemoresistant neuroblastoma cells. METHODS: We utilised cisplatin-adapted neuroblastoma cell lines as well as patient tissues before and after relapse to study alterations of BCL2 proteins upon chemoresistance. RESULTS: In a direct comparison of cisplatin-resistant cells we identified a prominent loss of sensitivity to BCL2/BCL-XL inhibitors that is associated with an increase in MCL1 dependency and high expression of MCL1 in patient tumour tissues...

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