A5075056823- Advanced NMR Techniques and Applications
- Medical Imaging Techniques and Applications
- Enzyme function and inhibition
- Chromatin Remodeling and Cancer
- Prostate Cancer Treatment and Research
- Amino Acid Enzymes and Metabolism
- Hormonal and reproductive studies
- Advanced MRI Techniques and Applications
- Molecular spectroscopy and chirality
- Estrogen and related hormone effects
- Cancer, Hypoxia, and Metabolism
- Cancer-related gene regulation
- Radiomics and Machine Learning in Medical Imaging
- Inflammatory mediators and NSAID effects
- HER2/EGFR in Cancer Research
- Sarcoma Diagnosis and Treatment
- Viral Infections and Vectors
- Influenza Virus Research Studies
- Pharmacology and Obesity Treatment
- Digestive system and related health
- Cancer therapeutics and mechanisms
- Cancer-related Molecular Pathways
- Cell Adhesion Molecules Research
- Leptospirosis research and findings
- Pediatric Pain Management Techniques
University of Cambridge
2013-2025
Cancer Research UK
2008-2024
Lymphatic Education & Research Network
2024
Alzheimer’s Research UK
2024
Cancer Research UK Cambridge Center
2013-2019
Animal Health Trust
2005-2013
Cambridge University Hospitals NHS Foundation Trust
2013
Abbott Fund
2011
University College London
2008
Solvay (United States)
2005-2008
Four-stranded G-quadruplex DNA secondary structures have recently been visualized in the nuclei of human cultured cells. Here, we show that BG4, a G-quadruplex-specific antibody, can be used to stain patient-derived tissues using immunohistochemistry. We observe significantly elevated number G-quadruplex-positive cancers liver and stomach as compared background non-neoplastic tissue. Our results suggest formation detected measured material may characteristic some cancers.
Abstract We retrospectively demonstrated that an outbreak of severe respiratory disease in a pack English foxhounds the United Kingdom September 2002 was caused by equine influenza A virus (H3N8). also canine tissue possesses relevant receptors for infection with virus.
Abstract Human mRNA DeXD/H-box helicases are ubiquitous molecular motors that required for the majority of cellular processes involve RNA metabolism. One most abundant is eIF4A, which during initiation phase protein synthesis to unwind regions highly structured would otherwise impede scanning ribosome. Dysregulation associated with tumorigenesis, but little known about detailed relationships between helicase function and malignant phenotype in solid malignancies. Therefore,...
Estrogen Receptor-β (ERβ) has been implicated in many cancers. In prostate and breast cancer its function is controversial, but genetic studies implicate a role progression. Much of the confusion around ERβ stems from antibodies that are inadequately validated, yet have become standard tools for deciphering role. Using an ERβ-inducible cell system we assessed commonly utilized show one most used antibodies, NCL-ER-BETA, non-specific ERβ. Other limited specificity or only specific...
Abstract Hyperpolarised magnetic resonance imaging (HP 13 C-MRI) is an emerging clinical technique to detect [1- C]lactate production in prostate cancer (PCa) following intravenous injection of hyperpolarised C]pyruvate. Here we differentiate clinically significant PCa from indolent disease a low/intermediate-risk population by correlating labelling on MRI with the percentage Gleason pattern 4 (%GP4) disease. Using immunohistochemistry and spatial transcriptomics, show that HP C-MRI...
Pancreatic ductal adenocarcinoma (PDA) is a highly lethal disease that refractory to medical intervention. Notch pathway antagonism has been shown prevent pancreatic preneoplasia progression in mouse models, but potential benefits the setting of an established PDA tumor have not established. We demonstrate gamma secretase inhibitor MRK003 effectively inhibits intratumoral signaling KPC model advanced PDA. Although monotherapy fails extend lifespan mice, combination with chemotherapeutic...
The androgen receptor (AR) is the dominant growth factor in prostate cancer (PCa). Therefore, understanding how ARs regulate human transcriptome of paramount importance. early effects castration on PCa have not previously been studied 27 patients medically castrated with degarelix 7 d before radical prostatectomy. We used mass spectrometry, immunohistochemistry, and gene expression array (validated by reverse transcription-polymerase chain reaction) to compare resected tumour matched,...
The purpose of this study was to evaluate the pharmacokinetic profile intranasal lorazepam in comparison currently established administration routes. Eleven healthy volunteers completed randomized crossover study. On three occasions, each separated by a 1-week washout, subjects received 2 mg dose via intranasal, intravenous, or intramuscular route. Blood samples were collected serially from 0 36 hours. Noncompartmental methods used determine parameters. Lorazepam well absorbed following with...
Abstract Metabolic imaging has been widely used to measure the early responses of tumors treatment. Here, we assess abilities PET measurement [18F]FDG uptake and MRI hyperpolarized [1-13C]pyruvate metabolism detect changes in glycolysis following treatment-induced cell death human colorectal (Colo205) breast adenocarcinoma (MDA-MB-231) xenografts mice. A TRAIL agonist that binds but not mouse cells induced tumor-selective death. Tumor was assessed by injecting [1,6-13C2]glucose measuring...
Abstract Carbonic anhydrase buffers tissue pH by catalyzing the rapid interconversion of carbon dioxide (CO2) and bicarbonate (HCO3−). We assessed functional activity CAIX in two colorectal tumor models, expressing different levels enzyme, measuring rate exchange hyperpolarized 13C label between (H13CO3−) (13CO2), following injection H13CO3−, using 13C-magnetic resonance spectroscopy (13C-MRS) magnetization transfer measurements. 31P-MRS measurements chemical shift probe,...
Cancer driver mutations are defined by their high prevalence in cancers and presumed rarity normal tissues. However, recent studies show that positive selection epithelia can increase the of some cancer drivers. To determine true cancer-driving potential, it is essential to evaluate how frequent these tissues what phenotypes. Here, we explore bioavailability somatic variants quantifying age-related mutational burdens human colonic epithelium using immunodetection FFPE samples (N = 181...
Abstract Transcriptomic studies have attempted to classify glioblastoma (GB) into subtypes that predict survival and different therapeutic vulnerabilities 1–3 . Here we identified three metabolic subtypes: glycolytic, oxidative a mix of glycolytic oxidative, using mass spectrometry imaging rapidly excised tumour sections from two patients with GB who were infused [U- 13 C]glucose spatial transcriptomic analysis contiguous sections. The phenotypes are not correlated microenvironmental...
To evaluate the pharmacokinetics of haloperidol after intranasal administration compared with intravenous and intramuscular administration, to systemic local tolerance administration.Randomized, open-label, three-way crossover study.Academic medical center.Four healthy volunteers (two men, two women; aged 24-37 yrs).Each subject received in a randomized order following three treatments, 2-week washout period between treatments: 2.5 mg (0.5 ml 5.0 mg/ml) infused over 15 minutes, mg/ml), (2.5...
Abstract Hyperpolarised magnetic resonance imaging (HP- 13 C-MRI) has shown promise as a clinical tool for detecting and characterising prostate cancer. Here we use range of spatially resolved histological techniques to identify the biological mechanisms underpinning differential [1- C]lactate labelling between benign malignant prostate, well in tumours containing cribriform non-cribriform Gleason pattern 4 disease. show that elevated hyperpolarised signal cancer compared is primarily driven...
Abstract Breast cancer risk factors and clinical outcomes vary by tumour marker expression. However, individual studies often lack the power required to assess these relationships, large‐scale analyses are limited need for high throughput, standardized scoring methods. To address limitations, we assessed whether automated image analysis of immunohistochemically stained tissue microarrays can permit rapid, markers from multiple studies. Tissue microarray sections prepared in nine containing...
Cell death is an important target for imaging the early response of tumors to treatment. We describe here validation a phosphatidylserine-binding agent detecting tumor cell in vivo based on C2A domain synaptotagmin-I. <b>Methods:</b> The capability near-infrared fluorophore-labeled and <sup>99m</sup>Tc- <sup>111</sup>In-labeled derivatives C2Am death, using planar fluorescence SPECT, respectively, was evaluated implanted genetically engineered mouse models lymphoma human colorectal...
The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it less useful for grade 2 MCTs because they exhibit considerable variation biological behavior. In this retrospective study, immunohistochemical staining Ki-67, proliferating nuclear antigen (PCNA), and survivin a standardized argyrophilic nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin-embedded specimens canine MCTs, which...
The development of divinylpyrimidine (DVP) reagents for the synthesis antibody–drug conjugates (ADCs) with in vivo efficacy and tolerability is reported.
Abstract Objective: To investigate whether cyclooxygenase‐2 (COX‐2) is expressed by equine ocular and adnexal squamous cell carcinomas (SCC). Methods: Forty‐three samples of histologically confirmed cases SCC or carcinoma in situ (CIS) from 34 horses presented to the Animal Health Trust between 1992 2004 were subjected a standard, two‐layered, indirect immunohistochemical method using rabbit polyclonal antihuman COX‐2 antibody. Ten formalin‐fixed, paraffin‐embedded tissue taken recognized...