A5083795785- MicroRNA in disease regulation
- Testicular diseases and treatments
- Cancer-related molecular mechanisms research
- Circular RNAs in diseases
- Cervical Cancer and HPV Research
- Sarcoma Diagnosis and Treatment
- Protein Degradation and Inhibitors
- Extracellular vesicles in disease
- Brain Metastases and Treatment
- Receptor Mechanisms and Signaling
- Advanced biosensing and bioanalysis techniques
- RNA Research and Splicing
- Gestational Trophoblastic Disease Studies
- Cancer Genomics and Diagnostics
- Drug Transport and Resistance Mechanisms
- Molecular Biology Techniques and Applications
- Hepatitis B Virus Studies
- Histiocytic Disorders and Treatments
- Meningioma and schwannoma management
- RNA Interference and Gene Delivery
- Anodic Oxide Films and Nanostructures
- Glioma Diagnosis and Treatment
- Viral-associated cancers and disorders
- Pharmacogenetics and Drug Metabolism
- Toxoplasma gondii Research Studies
University of Cambridge
1977-2024
University of Ulster
2013
Addenbrooke's Hospital
2013
Royal Victoria Hospital
2013
European Bioinformatics Institute
2013
Medical Research Council
2010
An important event in the development of cervical squamous cell carcinoma (SCC) is deregulated expression high-risk human papillomavirus (HR-HPV) oncogenes, most commonly related to viral integration into host DNA. Mechanisms approximately 15% SCCs that contain extrachromosomal (episomal) HR-HPV are poorly understood due limited longitudinal data. We therefore used W12 model study mechanisms carcinogenesis associated with episomal HPV16. In vitro progression normally occurs through selection...
Abstract Despite their clinicopathologic heterogeneity, malignant germ cell tumors (GCT) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of downregulation let-7 family tumor suppressor microRNAs in GCTs. Microarray results from pediatric and adult samples (n = 45) showed LIN28, negative regulator biogenesis, was abundant GCTs, regardless patient age, site, or histologic subtype. Indeed, a strong correlation...
The current biomarkers alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) have limited sensitivity/specificity for diagnosing malignant germ cell tumors (GCTs) "marker-negative" patients require histological confirmation diagnosis. However, GCTs at intracranial sites are surgically relatively inaccessible biopsy carries risks. MicroRNAs from the miR-371~373 miR-302/367 clusters over-expressed in all and, particular, miR-371a-3p shows elevated serum levels diagnosis testicular...
In cervical carcinomas, high-risk human papillomavirus (HR-HPV) may be integrated into host chromosomes or remain extra-chromosomal (episomal). We used the W12 keratinocyte model to investigate effects of HPV16 early gene depletion on in vitro carcinogenesis pathways, particularly shared by cells with episomal versus DNA. Importantly, we were able study specific cellular consequences viral using short interfering RNAs known not cause phenotypic transcriptional off-target keratinocytes. found...
1 The binding of ligands to muscarinic receptors in intact longitudinal muscle strips from guinea-pig small intestine has been determined by measuring the inhibition irreversible [3H]-propylbenzilylcholine mustard ([3H]-PrBCM). 2 IC50 values for [3H]-PrBCM a given ligand were generally higher than those reported broken-cell preparations. This effect is probably due, at least part, presence an access-limitation factor kinetics tissue. 3 mean Hill coefficients antagonist approached unity, but...
Abstract Background: Quantifying circulating nucleic acids is an important new approach to cancer diagnosis/monitoring. Methods: We compared the suitability of serum versus plasma for measuring miRNAs using qRT-PCR and assessed how preanalytic variables that can affect tumor DNA (ctDNA) quantification in also influence miRNA levels. Results: Across 62 blood-derived specimens, samples EDTA, Streck-DNA, Streck-RNA tubes showed significantly higher Ct values multiple housekeeping miRNAs, with...
Cervical carcinogenesis is characterized by a clonal selection process in which the high-risk human papillomavirus (HRHPV) genome usually changes from extra-chromosomal (episomal) state seen productive infections to DNA that integrated into host chromosomes. However, it not clear whether all HRHPV integration events provide cells with selective growth advantage compared episome-containing they originate. It also unclear of containing particular integrant mixed population simply reflects...
When designing therapeutic short-interfering RNAs (siRNAs), off-target effects (OTEs) are usually predicted by computational quantification of messenger (mRNAs) that contain matches to the siRNA seed sequence in their 3' UTRs. It is assumed higher number transcriptional OTEs, greater size actual OTE signature and more detrimental phenotypic consequences target-negative cells.We tested this general assumption investigating OTEs potential siRNAs targeting human papillomavirus (HPV) type-16 E7...
Germ-cell-tumours (GCTs) are heterogeneous and management is complex. The current conventional biomarkers, alpha-fetoprotein human-chorionic-gonadotropin (HCG), have limited utility for diagnosis/follow-up as secretion restricted to specific malignant-GCT subtypes long half-life can make interpretation clinical decision-making challenging. We sought identify circulating microRNAs that reflected choriocarcinoma disease activity more accurately than HCG in a metastatic primary mediastinal...
Abstract BACKGROUND In Europe, bifocal germinoma is diagnosed based on typical age (>8-10y), symptoms (diabetes insipidus), radiological appearances, and serum/CSF AFP/HCG markers below thresholds. A 12yo male presented with 4-month headaches, 3-month polyuria/polydipsia, visual somnolence/memory issues. Weight=71.1kg; height=166cm. MRI head/spine revealed hydrocephalus 19×14×15mm (volume=2.09cm3) enhancing pineal lesion nodular suprasellar septum-pellucidum soft tissue. CSF positive...
Abstract Background MiR-371~373 and miR-302/367 cluster over-expression occurs in all malignant germ cell tumours (GCTs), regardless of age (paediatric/adult), site (gonadal/extragonadal), or subtype [seminoma, yolk sac tumour (YST), embryonal carcinoma (EC)]. Six eight microRNAs from these clusters contain the seed sequence ‘AAGUGC’, determining mRNA targeting. Here we sought to identify significance observations by targeting functionally. Methods We targeted miR-371~373 and/or GCT lines,...
Malignant germ-cell-tumours (GCTs) are characterised by microRNA (miRNA/miR-) dysregulation, with universal over-expression of miR-371~373 and miR-302/367 clusters regardless patient age, tumour site, or subtype (seminoma/yolk-sac-tumour/embryonal carcinoma). These miRNAs released into the bloodstream, presumed within extracellular-vesicles (EVs) represent promising biomarkers. Here, we comprehensively examined role EVs, their miRNA cargo, on (fibroblast/endothelial/macrophage) cells...
MicroRNAs (miRNAs) are short, nonprotein-coding RNAs, and their expression is dysregulated in malignant germ cell tumors (GCTs). Here, we investigated the causes consequences of downregulated miR-99a-5p/miR-100-5p (functionally identical) miR-125b-5p levels GCTs regardless age, site, or subtype. Quantitative RT-PCR was used to assess miR-99a-5p/miR-100-5p, miR-125b-5p, associated gene GCT tissues/cell lines [seminoma (Sem), yolk sac tumor (YST), embryonal carcinoma (EC)]. Cells were treated...
Patients presenting with diabetes insipidus (DI) and subtle pituitary-stalk thickening on MRI represent a management challenge. LCH germinoma work-up (including serum/CSF AFP/HCG) is usually negative, given the poor sensitivity of these tests. Risks neurosurgical biopsy in such cases often outweigh perceived benefits. Consequently, only performed for radiological progression. This suboptimal approach may cause diagnostic delay inferior outcomes. Non-invasive microRNA testing malignant germ...
<p>PDF - 59K.</p>
<p>PDF - 492K, Supplementary Figure 1: Levels of the nine members let-7 family in pediatric malignant-GCTs. 2: PCR quantification let-7e, LIN28 and LIN28B malignant-GCTs.Supplementary 3: Sylamer analysis up-regulated genes adult 4: Correlations between levels mRNA targets. 5: HMGA2 6: validation expression selected targets 7: Effects depletion malignant-GCT cells. 8: Independent confirmation specific effects 9: let-7e mimic 10: Relationships MYCN C-MYC versus 11: malignant-GCTs (S11)....
<div>Abstract<p>Despite their clinicopathologic heterogeneity, malignant germ cell tumors (GCT) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of downregulation <i>let-7</i> family tumor suppressor microRNAs in GCTs. Microarray results from pediatric and adult samples (<i>n</i> = 45) showed <i>LIN28</i>, negative regulator biogenesis, was abundant GCTs,...
<div>Abstract<p>Despite their clinicopathologic heterogeneity, malignant germ cell tumors (GCT) share molecular abnormalities that are likely to be functionally important. In this study, we investigated the potential significance of downregulation <i>let-7</i> family tumor suppressor microRNAs in GCTs. Microarray results from pediatric and adult samples (<i>n</i> = 45) showed <i>LIN28</i>, negative regulator biogenesis, was abundant GCTs,...
<p>PDF - 59K.</p>
<p>PDF - 492K, Supplementary Figure 1: Levels of the nine members let-7 family in pediatric malignant-GCTs. 2: PCR quantification let-7e, LIN28 and LIN28B malignant-GCTs.Supplementary 3: Sylamer analysis up-regulated genes adult 4: Correlations between levels mRNA targets. 5: HMGA2 6: validation expression selected targets 7: Effects depletion malignant-GCT cells. 8: Independent confirmation specific effects 9: let-7e mimic 10: Relationships MYCN C-MYC versus 11: malignant-GCTs (S11)....