Translation of PET radiotracers for cancer imaging: recommendations from the National Cancer Imaging Translational Accelerator (NCITA) consensus meeting.

Background: The clinical translation of positron emission tomography (PET) radiotracers for cancer management presents complex challenges. We have developed consensus-based recommendations for preclinical and clinical assessment of novel and established radiotracers, applied to image different cancer types, to improve the standardisation of translational methodologies and accelerate clinical implementation.

Methods: A consensus process was developed using the RAND/UCLA Appropriateness Method (RAM) to gather insights from a multidisciplinary panel of 38 key stakeholders on the appropriateness of preclinical and clinical methodologies and stakeholder engagement for PET radiotracer translation.

Retrospective Cohort Study: Scope for Improvement-Barriers to Post-Polypectomy Surveillance in the Integrated Technologies for Improved Polyp Surveillance Cohort.

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.

Raman active diyne-girder conformationally constrained p53 stapled peptides bind to MDM2 for visualisation without fluorophores.

Peptide stapling is an effective strategy to stabilise α-helical peptides, enhancing their bioactive conformation and improving physiochemical properties. In this study, we apply our novel diyne-girder stapling approach to the MDM2/MDMX α-helical binding region of the p53 transactivation domain. By incorporation of an unnatural amino acid to create an optimal , + 7 bridge length, we developed a highly α-helical stapled peptide, 4, confirmed circular dichroism.

Hydrogel models of pancreatic adenocarcinoma to study cell mechanosensing.

Pancreatic adenocarcinoma (PDAC) is the predominant form of pancreatic cancer and one of the leading causes of cancer-related death worldwide, with an extremely poor prognosis after diagnosis. High mortality from PDAC arises partly due to late diagnosis resulting from a lack of early-stage biomarkers and due to chemotherapeutic drug resistance, which arises from a highly fibrotic stromal response known as desmoplasia. Desmoplasia alters tissue mechanics, which triggers changes in cell mechanosensing and leads to dysregulated transcriptional activity and disease phenotypes.

Impact of Centralisation of Radical Prostatectomy Driven by the Introduction of Robotic Systems on Positive Surgical Margin and Biochemical Recurrence in pT2 Prostate Cancer.

Background: To assess how centralisation of cancer services via robotic surgery influenced positive surgical margin (PSM) occurrence and its associated risk of biochemical recurrence (BCR) in cases of pT2 prostate cancer (PC).

Methods: Retrospective analysis of all radical prostatectomy (RP) cases performed in the West of Scotland during the period from January 2013 to June 2022. Primary outcomes were PSM and BCR.

UNC119 regulates T-cell receptor signalling in primary T cells and T acute lymphocytic leukaemia.

T-cell receptor recognition of cognate peptide-MHC leads to the formation of signalling domains and the immunological synapse. Because of the close membrane apposition, there is rapid exclusion of CD45, and therefore LCK activation. Much less is known about whether spatial regulation of the intracellular face dictates LCK activity and TCR signal transduction.

The impact of neoadjuvant therapy in patients with left-sided resectable pancreatic cancer: an international multicenter study.

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.

Visualizing Cancer Heterogeneity at the Molecular and Cellular Levels: Lessons from Rosetta.

Understanding tumor heterogeneity is a major challenge that was recognized as one of the first Cancer Grand Challenges, with a call to provide solutions to visualize tumor heterogeneity. The Rosetta team took on this challenge, exploiting advances in spatial-omics approaches centered around mass spectrometry imaging to map tumor heterogeneity at the cellular and molecular scales with different levels of resolution. See related article by Bressan et al.

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

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.

Assessment of a 6-arylaminobenzamide lead derivative as a potential core scaffold for S1P positron emission tomography radiotracer development.

Sphingosine-1-phosphate-5 receptors (S1P) are predominantly expressed in oligodendrocytes and as a result have been proposed as an important target in Multiple Sclerosis (MS). Selective S1P radiotracers could enable in vivo positron emission tomography (PET) imaging of oligodendrocytes activity. Here we report the synthesis, radiolabelling and first preclinical evaluation of the pharmacokinetics and binding properties of a lead 6-arylaminobenzamide derivative, 6-(mesitylamino)-2-methoxy-3-methylbenzamide (also named as TEFM180), as a potential core scaffold for development of novel S1P PET radiotracers.

Learning from Other Tumors: Pathways for Progress and Overcoming Challenges in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a group of complex and heterogeneous tumors originating from the epithelial cells of bile ducts that can occur in intrahepatic, perihilar, or distal localizations [...

A reproducibility study on invasion in small pulmonary adenocarcinoma according to the WHO and a modified classification, supported by biomarkers.

Objectives: Evaluating invasion in non-mucinous adenocarcinoma (NMA) of the lung is crucial for accurate pT-staging. This study compares the World Health Organization (WHO) with a recently modified NMA classification.

Materials And Methods: A retrospective case-control study was conducted on small NMA pT1N0M0 cases with a 5-year follow-up.

The adaptor protein Miro1 modulates horizontal transfer of mitochondria in mouse melanoma models.

Recent research has shown that mtDNA-deficient cancer cells (ρ cells) acquire mitochondria from tumor stromal cells to restore respiration, facilitating tumor formation. We investigated the role of Miro1, an adaptor protein involved in movement of mitochondria along microtubules, in this phenomenon. Inducible Miro1 knockout (Miro1) mice markedly delayed tumor formation after grafting ρ cancer cells.

Frozen Section Doughnuts Obtained with a 5 mm Stapling Device Improve Outcomes in Laparoscopic Endorectal Pull-Throughs for Hirschsprung's Disease.

A primary pull-through for Hirschsprung's disease (HD) requires confirmation of normal ganglionic bowel by intraoperative biopsies to determine the level of resection. Despite this, aganglionic bowel that is not fully resected (so-called "transition zone pull-throughs") is reported in 15%-19% of patients. We hypothesize that this may result from insufficient biopsies sent for intraoperative diagnosis.

Comparative Analysis of Transcriptomic and Proteomic Expression between Two Non-Small Cell Lung Cancer Subtypes.

Non-small cell lung cancer (NSCLC) is frequently diagnosed late and has poor survival. The two predominant subtypes of NSCLC, adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC), are currently differentially diagnosed using immunohistochemical markers; however, they are increasingly recognized as very different cancer types suggestive of potential for new, more targeted therapies. There are extensive efforts to find more precise and noninvasive differential diagnostic tools.

IL6 and IL6R as Prognostic Biomarkers in Colorectal Cancer.

Colorectal cancer is the third most diagnosed malignancy worldwide and survival outcomes remain poor. Research is focused on the identification of novel prognostic and predictive biomarkers to improve clinical practice. There is robust evidence in the literature that inflammatory cytokine interleukin-6 (IL6) is elevated systemically in CRC patients and that this phenomenon is a predictor of poor survival outcome.

Laryngeal Cancer in the West of Scotland 2014-2020: Trends and Survival in a Cohort of 867 Patients.

Background: Laryngeal squamous cell cancer (LSCC) accounts for around one-third of head and neck cancers, with smoking and alcohol as major risk factors. Despite advances in organ preservation, survival rates have stagnated globally over recent decades. The impact of socioeconomic deprivation on LSCC outcomes in the West of Scotland remains underexplored.

Single cell and spatial analysis of immune-hot and immune-cold tumours identifies fibroblast subtypes associated with distinct immunological niches and positive immunotherapy response.

Cancer-associated Fibroblasts (CAFs) have emerged as critical regulators of anti-tumour immunity, with both beneficial and detrimental properties that remain poorly characterised. To investigate this, we performed single-cell and spatial transcriptomic analysis, comparing head & neck squamous cell carcinoma (HNSCC) subgroups, which although heterogenous, can be considered broadly immune-hot and immune-cold (human papillomavirus [HPV]+ve and HPV-ve tumours respectively). This identified six fibroblast subpopulations, including two with immunomodulatory gene expression profiles (IL-11 + inflammatory [i]CAF and CCL19 + fibroblastic reticular cell [FRC]-like).

Enterocyte-like differentiation defines metabolic gene signatures of CMS3 colorectal cancers and provides therapeutic vulnerability.

Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify the underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed.

Cholangiocarcinoma Targeted Therapies: Mechanisms of Action and Resistance.

Cholangiocarcinoma is an aggressive bile duct malignancy with heterogeneous genomic features. Although most patients receive standard-of-care chemotherapy/immunotherapy, genomic changes that can be targeted with established or emerging therapeutics are common. Accordingly, precision medicine strategies are transforming the next-line treatment for patient subsets.

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

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.

Developing a 3D bone model of osteosarcoma to investigate cancer mechanisms and evaluate treatments.

Osteosarcoma is the most common primary bone cancer, occurring frequently in children and young adults. Patients are treated with surgery and multi-agent chemotherapy, and despite the introduction of mifamurtide in 2011, there has been little improvement in survival for decades. 3-dimensional models offer the potential to understand the complexity of the osteosarcoma tumor microenvironment and aid in developing new treatment approaches.

The association between animal protein, plant protein, and their substitution with bladder cancer risk: a pooled analysis of 10 cohort studies.

Purpose: Although total dietary protein intake has been associated with bladder cancer (BC) risk, the effect of the origin (plant or animal) and the substitutions remain to be understood. This study aimed to investigate the effect of total dietary protein, animal-based protein, plant-based protein, and their substitutions with each other on the risk of BC using a pooled analysis of 10 cohort studies.

Methods: The study was conducted within the "BLadder cancer Epidemiology and Nutritional Determinants" (BLEND) study, including 10 prospective cohort studies from several European countries, the United Kingdom, and the United States.