A5009329806- Cancer Genomics and Diagnostics
- Cancer Immunotherapy and Biomarkers
- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Lung Cancer Treatments and Mutations
- Genital Health and Disease
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Hemoglobinopathies and Related Disorders
- Prostate Cancer Treatment and Research
- Viral Infections and Immunology Research
- Pancreatic and Hepatic Oncology Research
- Glioma Diagnosis and Treatment
- Renal and related cancers
- Urologic and reproductive health conditions
- Hepatocellular Carcinoma Treatment and Prognosis
- Prostate Cancer Diagnosis and Treatment
- Iron Metabolism and Disorders
- Ovarian cancer diagnosis and treatment
- Lymphoma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Genetic factors in colorectal cancer
- Liver physiology and pathology
- Colorectal Cancer Treatments and Studies
University of Trieste
2025
Politecnico di Milano
2024
Roche (Switzerland)
2024
University College London
2006-2023
Wolfson Foundation
2010-2023
Cancer Institute (WIA)
2009-2023
CRUK Lung Cancer Centre of Excellence
2014-2018
CellCentric (United Kingdom)
2016
Cancer Research UK
2016
University College Hospital
2009-2013
The origin licensing factors minichromosome maintenance 2 (Mcm2) and Geminin have recently been identified as critical regulators of growth differentiation. Here we investigated the regulation these together with Ki67 to further elucidate cell cycle kinetics renal carcinoma (RCC). Furthermore, examined role Ki67, Mcm2, in disease-free survival after nephrectomy patients localized RCC.Tissue sections from 176 radical specimens were immunohistochemically stained Geminin, antibodies. Labeling...
Multiparameter analysis of core regulatory proteins involved in G1–S and G2–M cell-cycle transitions provides a powerful biomarker readout for assessment the state. We have applied this algorithm to breast cancer investigate how cell cycle impacts on disease progression. Protein expression profiles key constituents DNA replication licensing pathway (Mcm2, geminin) mitotic machinery (Plk1, Aurora A substrate histone H3S10ph) were generated cohort 182 patients linked clinicopathological...
There is a lack of prognostic and predictive biomarkers in epithelial ovarian carcinoma, the targeting oncogenic signaling pathways has had limited impact on patient survival this highly heterogeneous disease. The origin licensing machinery, which renders chromosomes competent for DNA replication, acts as convergence point upstream pathways. We tested hypothesis that Cdc7 kinase, core component clinical outcome may constitute novel therapeutic target carcinoma.A total 143 cases cancer 5...
Mcm2–7 (MCM) proteins are part of the origin licensing machinery that regulates initiation DNA replication. Geminin is a repressor and prevents reinitiation replication during S–G2–M phase by blocking reloading at origins. Here, we have analysed these factors (RLFs) to determine whether pathway becomes deregulated mammary carcinogenesis, assessed their potential value as prognostic markers. Protein expression profiles were generated for Ki67, Mcm2, geminin, HER-2, ER PR in series reduction...
The DNA replication (or origin) licensing system ensures precise duplication of the genome in each cell cycle and is a powerful regulator proliferation metazoa. Studies yeast, Drosophila melanogaster Xenopus laevis have characterised molecular machinery that constitutes system, but it remains to be determined how this important evolutionary conserved pathway regulated Homo sapiens. We investigated regulation origin factors Cdc6, Cdt1, Mcm2 Geminin human somatic germ cells. Cdc6 Cdt1 play an...
Mandatory Day 2 and 8 PCR testing variant sequencing of international arrivals has been recently introduced by the UK Government to mitigate against cross-border transmission high-risk SARS-CoV-2 variants.SARS-CoV-2 combines TaqPath CE-IVD COVID-19 RT-PCR with Ion AmpliSeq Next Generation Sequencing Assay. Retrospective analysis test trending data was performed from initiation on 11th March through 14th April 2021.During this time interval, 203,065 tests were performed, 3,855 samples...
Abstract Purpose: DNA replication licensing factors and Aurora kinases play critical roles in maintaining genomic integrity. We used multiparameter analyses of these cell cycle regulatory proteins to investigate their role the progression epithelial ovarian carcinoma (EOC). Experimental Design: In a cohort 143 patients, we linked protein expression profiles proliferation marker Ki67, Mcm2 geminin, A B tumor ploidy status clinical outcome. Results: Mcm2, are significantly associated with...
Activation of mitogen/extracellular-signal-regulated kinase 5/extracellular signal-regulated kinase-5 (MEK5/ERK5) growth signalling is coupled to increased cell proliferation in prostate cancer (PCa). Dysregulation the DNA replication licensing pathway, a critical step control downstream transduction pathways, associated with development PCa. In this study we have investigated linkages between MEK5/ERK5 pathway and during carcinogenesis. The effects on expression factors Mcm2 geminin marker...
The DNA replication licensing machinery is integral to the control of proliferation, differentiation, and maintenance genomic stability in human cells. We have analyzed factors (RLF), together with ploidy status, investigate their role progression penile squamous cell carcinoma assess utility as novel prognostic tools.In a cohort 141 patients, we linked protein expression profiles standard proliferation marker Ki67 RLFs Mcm2 geminin clinicopathologic variables, clinical outcome.Increased...
Aberrant mitosis is a common feature of cancer, yet little known about the altered genes causing mitotic defects. We screened human tumours for cells with morphological signatures highly specific defects previously assigned to candidate in genome-wide RNA interference screen carried out HeLa (www.mitocheck.org). discovered striking enrichment early configurations indicative prophase/prometaphase delay breast cancer. Promoter methylation analysis MitoCheck corresponding 'mitotic delay' class...
// Matthew T. Huggett 1, 2 , Slavica Tudzarova Ian Proctor Marco Loddo 2, 3 Margaret G. Keane 1 Kai Stoeber Gareth H. Williams Stephen P. Pereira UCL Institute for Liver and Digestive Health Cancer Institute, University College London, UK The Research Department of Pathology, Oncologica Ltd, Science Village, Chesterford Park, Cambridge, Correspondence to: Williams, e-mail: gareth.williams@oncologica.com Keywords: pancreatic cancer, cell cycle, DNA replication, Cdc7 Received: July 22, 2015...
Abstract Peripheral B‐cell lymphomas representing 90% of lymphoid neoplasms are divided into low‐ and high‐growth fraction lymphomas. Here we investigate regulation DNA replication licensing during lymphomagenesis. Combined analysis origin factors Mcm2 geminin with the proliferation marker Ki67 in SLL/CLL, MCL, DLBCL Burkitt lymphoma reveals for first time precise cell cycle state these entities. Given that tight downregulation defines quiescent (G0) both high‐ low‐growth express Mcm2, data...
Olaparib is effective in metastatic triple negative breast cancer (TNBC) carrying germline mutations DNA damage repair (DDR) genes BRCA1/2 (gBRCA-mut). The OLTRE window-of-opportunity trial preliminarily investigated potential pathologic, radiometabolic and immune biomarkers of early-response to olaparib gBRCA-wild-type (wt) TNBC and, as proof-of-concept gBRCA-mut HER2-negative BC.Patients received for 3 weeks (3w) before standard neoadjuvant chemotherapy underwent multiple FDG18-PET/CT scan...
We investigated cell cycle kinetics of nodular lesions in cirrhosis to differentiate hepatocellular carcinoma (HCC) from its precursor lesions.Twelve small HCC, 10 regenerative (RN), six large (LRN), and five dysplastic nodules (DN), identified explant cirrhotic livers consecutive patients transplanted at Royal Free Hospital 2002. Immunoperoxidase for MCM2, geminin Ki67 was performed the percentage positive cells counted.The proportion expressing MCM2 more than those Ki67, which turn...
The VENTANA PD-L1 (SP263) Assay is approved for use with anti-programmed cell death-1/programmed death ligand-1 (PD-1/PD-L1) therapies in NSCLC and urothelial carcinoma. Here, we investigate interobserver reliability of the SP263 assay, applied to scoring tumor cells (TCs) NSCLC. Six practicing European pulmonary pathologists independently scored proportion TCs expressing (TC score) from 200 archival, commercially sourced, formalin-fixed paraffin-embedded resections stained using assay....
<h3>Aims</h3> Multiparameter analysis of cell cycle markers has shown a strong relationship between progression and tumor grade, stage, clinical outcome in penile, renal, ovarian, breast cancers. We sought to link expression phase–specific cervical cancer investigate their potential use as prognostic predictive markers. <h3>Methods</h3> Pretreatment biopsy material was obtained from 35 patients with (stage IB2-IVA) 12 normal cervix control cases. Each patient treated neoadjuvant chemotherapy...
The standard treatment for glioblastoma involves a combination of surgery, radiation and chemotherapy but have limited impact on survival. exponential increase in targeted agents directed at pivotal oncogenic pathways now provide new therapeutic opportunities this tumour type. However, lack comprehensive precision oncology testing diagnosis means such are potentially overlooked. To investigate the role semiconductor sequencing detection predictive biomarkers routine samples we undertaken...
e13642 Background: The recent exponential increase in targeted agents and immunotherapies provide new therapeutic opportunities for patients with advanced cancers who have failed first line therapy. However, lack of comprehensive precision oncology testing as part routine pathology assessment means potential are difficult to identify or remain undiscovered many patients. Methods: To address this unmet clinical need we established Oncofocus, a clinically validated, ISO15189/2012 CLIA...
Retrospective studies on male breast cancer (MBC) have suff ered from small numbers of cases available any one centre; thus a signifi cant problem in eff ectively studying this disease is accruing suffi ciently large to allow comparative analysis biomarkers associated with response.Using coordinated multicentre approach, we present the fi rst large-scale study address relevance expression hormone receptors MBC and female (FBC) using immunohistochemistry combined novel bioinformatics...
Medizinische Notfälle auf See sind immer eine Herausforderung. Besonders hoch die Anforderungen jedoch bei Notfällen Windkraftanlagen (WKA): Hier arbeiten nur kleine Teams und es gibt selten Räume für medizinische Behandlungen wie größeren Gas- oder Ölplattformen. Aufgrund von Notfällen, Staat WKA-Betreiber nicht ausreichend vorbereitet waren, wurden in den letzten Jahren unterschiedlichen Institutionen, auch ORS, viele notwendige Strukturen aufgebaut. Diese werden weiter optimiert, unter...