A5065916505- Cervical Cancer and HPV Research
- Testicular diseases and treatments
- Hepatitis B Virus Studies
- Sarcoma Diagnosis and Treatment
- MicroRNA in disease regulation
- Reproductive tract infections research
- Cancer-related molecular mechanisms research
- Molecular Biology Techniques and Applications
- Circular RNAs in diseases
- Mitochondrial Function and Pathology
- Liver Disease Diagnosis and Treatment
- Herpesvirus Infections and Treatments
- Vestibular and auditory disorders
- Virus-based gene therapy research
- Genetic Neurodegenerative Diseases
- Cancer Genomics and Diagnostics
- Protein Degradation and Inhibitors
- Pain Mechanisms and Treatments
- Viral-associated cancers and disorders
- Telomeres, Telomerase, and Senescence
- T-cell and Retrovirus Studies
- Hereditary Neurological Disorders
- Plant Disease Resistance and Genetics
- Neurological disorders and treatments
- Renal and related cancers
University of Cambridge
2015-2025
Medical Research Council
2008-2023
Ospedale Misericordia - Grosseto
2020
University of Rome Tor Vergata
2014
Royal Victoria Hospital
2013
University of Ulster
2013
Addenbrooke's Hospital
2013
European Bioinformatics Institute
2013
Hutchison/MRC Research Centre
2011-2012
MRC Cancer Unit
2012
Human papillomaviruses (HPV) activate a number of host factors to control their differentiation-dependent life cycles. The transcription factor signal transducer and activator (STAT)-3 is important for cell cycle progression survival in response cytokines growth factors. STAT3 requires phosphorylation on Ser727, addition Tyr705 be transcriptionally active. In this study, we show that essential the HPV undifferentiated differentiated keratinocytes. Primary human keratinocytes containing...
Abstract As the high-risk human papillomavirus (HPV) integrants seen in anogenital carcinomas represent end-point of a clonal selection process, we used W12 model to study naturally occurring integration events that exist HPV16-infected cervical keratinocytes before integrant selection. We performed limiting dilution cloning identify present cells also maintain episomes. Such arise natural context and noncompetitive environment, as they are transcriptionally repressed by episome-derived E2....
Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) germ cell tumor (GCT) pre-orchiectomy; however, its ability to detect occult disease is understudied. To refine serum assay minimal residual setting we compared raw (Cq) and normalized (∆Cq, RQ) values from prior assays, validated interlaboratory concordance by aliquot swapping. Revised was determined a cohort 32 patients suspected retroperitoneal disease. Assay superiority comparing resulting...
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...
Telomeres, a validated biomarker of aging, comprise multiple nucleotide repeats capping chromosomes that shorten with each cell cycle until critical length is achieved, precipitating senescence. Only two previous studies focused on the effect aging in “normal” liver tissue, but these were compromised by small sample size, limited age range, tissue derived from individuals an increased risk senescence, and use homogenates. We developed robust large-volume, four-color quantitative fluorescent...
Oncostatin M receptor (OSMR) is commonly over-expressed in advanced cervical squamous cell carcinoma (SCC), producing a significantly worse clinical outcome. Cervical SCC cells that over-express OSMR show enhanced responsiveness to the major ligand OSM, which induces multiple pro-malignant effects, including increased migration and invasiveness. Here, we tissue transglutaminase (TGM2) an important mediator of ligand-dependent phenotypic effects over-expression cells. TGM2 expression...
ABSTRACT A neonatal rat dorsal root ganglion-derived neuronal culture system has been utilized to study herpes simplex virus (HSV) latency establishment, maintenance, and reactivation. We present our initial characterization of viral gene expression in neurons following infection with replication-defective HSV recombinants carrying β-galactosidase and/or green fluorescent protein reporter genes under the control lytic cycle- or latency-associated promoters. In this promoter activity was...
Copy-number gain of the oncostatin-M receptor (OSMR) occurs frequently in cervical squamous cell carcinoma (SCC) and is associated with adverse clinical outcome. We previously showed that OSMR overexpression renders SCC cells more sensitive to major ligand (OSM), which increases migration invasion vitro. hypothesised a contribution this phenotype would come from epithelial-mesenchymal transition (EMT).We performed comprehensive integrated study, involving vitro line studies, vivo animal...
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...
Development of cervical cancer is directly associated with integration human papillomavirus (HPV) genomes into host chromosomes and subsequent modulation HPV oncogene expression, which correlates multi-layered epigenetic changes at the integrated genomes. However, process itself dysregulation gene expression sites in our model HPV16 integrant clone natural selection has remained enigmatic. We now show, using a state-of-the-art ‘HPV site capture’ (HISC) technique, that likely occurs through...
648 Background: MicroRNAs (mi-RNAs) have emerged as promising biomarkers for the detection of viable germ cell tumors (GCT). Our previous work in a research lab demonstrated optimal performance with positive results that had Cq values less than 28, an indeterminate range between 28-35 and negative greater 35. In this study, we assessed characteristics miR-371a-3p CLIA certified at UCSD. Methods: Due to workflows, equipment scaling, several modifications were required from our original...
Changes in the size of test components (R1 and R2) trigemino-facial reflex were studied after electrical subliminal conditioning stimulation applied to trigeminal, median sural nerves. After activation trigeminal nerve (below threshold), early R1 component showed phasic facilitation, peaking at about 50 ms interstimulus delay, followed by a long-lasting inhibition recovering 300-400 ms. The same resulted monotonic late R2, starting 15-20 ms, with maximum 100-150 lasting Intensity threshold...
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...
NUT carcinoma is challenging to diagnose and may mimic a germ cell tumor (GCT) due raised serum alpha-fetoprotein (AFP). A 15-year-old patient presented with back pain cough. Investigation revealed mediastinal mass multiple bone metastases. Serum AFP was highly elevated, consistent metastatic malignant nonseminomatous GCT. Aggressive chemotherapy initiated initial response, unfortunately not sustained. Diagnostic biopsy showed undifferentiated cells weak GCT immunophenotype but ultimately...
The oncostatin M (OSM) receptor (OSMR) shows frequent gene copy number gains and overexpression in cervical squamous cell carcinomas (SCCs), associated with adverse clinical outcomes. In SCC cells that overexpress OSMR, the major ligand OSM induces multiple pro-malignant effects, including invasion, secretion of angiogenic factors, metastasis. Here, we demonstrate, for first time, OSMR activates cell-autonomous feed-forward signalling, via further expression sustained STAT3 activation,...
• Evoked potentials are reported in 10 patients with cerebrotendinous xanthomatosis, eight of whom had peripheral neuropathy. Four subjects showed delayed N13 to N20 interpeak latencies for arm somatosensory evoked potentials, and five moderately prolonged I III V brain-stem auditory potentials. Six seven marked delay desynchronization visual All undergoing transcutaneous magnetic stimulation the motor cortex presented greatly central conduction time, especially lower limbs. After treatment...
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...
In cervical squamous cell carcinomas, high-risk human papillomavirus (HRHPV) DNA is usually integrated into host chromosomes. Multiple integration events are thought to be present within the cells of a polyclonal premalignant lesion and features that underpin clonal selection one particular integrant remain poorly understood. We previously used W12 model system generate panel keratinocyte clones, derived from low-grade naturally infected with major HRHPV type, HPV16. The were isolated...
A neurophysiological study of 11 patients belonging to 5 families affected by Leber's hereditary optic atrophy is reported. Electromyography, nerve conduction velocities and somatosensory evoked potentials were normal. Visual absent or delayed, desynchronized reduced in amplitude. Brainstem auditory anomalous 64% subjects all without hearing defects. These changes which have never before been reported, confirm multisystem involvement this disease.