A5038850730- Ovarian cancer diagnosis and treatment
- PARP inhibition in cancer therapy
- BRCA gene mutations in cancer
- Endometrial and Cervical Cancer Treatments
- Cancer Genomics and Diagnostics
- DNA Repair Mechanisms
- Estrogen and related hormone effects
- CRISPR and Genetic Engineering
- COVID-19 and healthcare impacts
- Genetic factors in colorectal cancer
- Endometriosis Research and Treatment
- Cervical Cancer and HPV Research
- Uterine Myomas and Treatments
- Cancer-related molecular mechanisms research
- Intraperitoneal and Appendiceal Malignancies
- Cancer Risks and Factors
- Plant Virus Research Studies
- Integrated Circuits and Semiconductor Failure Analysis
- Cancer-related Molecular Pathways
- Cancer, Lipids, and Metabolism
- Renal cell carcinoma treatment
- Reproductive Biology and Fertility
- Cardiac, Anesthesia and Surgical Outcomes
- Global Cancer Incidence and Screening
- Trauma and Emergency Care Studies
Manchester University NHS Foundation Trust
2017-2025
University of Manchester
2016-2025
University of Arkansas for Medical Sciences
2016-2025
Manchester Academic Health Science Centre
2015-2024
St Mary's Hospital
2015-2024
Cancer Research UK Manchester Institute
2014-2024
Weatherford College
2024
University Hospital Southampton NHS Foundation Trust
2024
Newcastle University
2006-2023
Queen Elizabeth Hospital
2005-2023
The randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus alone (RT) for women with high-risk endometrial cancer (EC). Because Genome Atlas defined an EC molecular classification strong prognostic value, we prognosis impact each subgroup using tissue samples from PORTEC-3 participants.Paraffin-embedded tissues 423 consenting patients...
Abstract Purpose: Poly(ADP-ribose) polymerase (PARP) inhibitors selectively target homologous recombination (HR)–defective cells and show good clinical activity in hereditary breast ovarian cancer associated with BRCA1 or BRCA2 mutations. A high proportion (up to 50%) of sporadic epithelial cancers (EOC) could be deficient HR due genetic epigenetic inactivation BRCA1/BRCA2 other genes. Therefore, there is a potential for extending the use PARP these patients if status can identified. We...
Mutations in BRCA1 and BRCA2 (BRCA1/2), components of the homologous recombination DNA repair (HRR) pathway, are associated with hereditary breast ovarian cancers. Poly(ADP-ribose) polymerase (PARP) inhibitors selectively cytotoxic to animal cells defective HRR, but results human cancer have been contradictory. We undertook, our knowledge, first comprehensive vitro vivo investigations antitumor activity PARP inhibitor AG014699 carrying mutated or epigenetically silenced BRCA1/2. used nine...
There are no internationally agreed upon clinical guidelines as to which women with gynecological cancer would benefit from Lynch syndrome screening or how best manage the risk of in syndrome. The Manchester International Consensus Group was convened April 2017 address this unmet need. aim develop clear and comprehensive guidance regarding management sequelae based on existing evidence expert opinion medical professionals patients.
Standard molecular classification of endometrial cancers (EC) is now endorsed by the WHO and identifies p53-abnormal (p53abn) EC as subgroup with poorest prognosis most likely to benefit from adjuvant chemo(radio)therapy. P53abn are POLE wildtype, mismatch repair proficient show abnormal immunohistochemical (IHC) staining for p53. Correct interpretation routinely performed p53 IHC has therefore become paramount importance. We aimed comprehensively investigate patterns their relation...
The ataxia telangiectasia mutated and Rad3-related kinase (ATR) has a key role in the signalling of stalled replication forks DNA damage to cell cycle checkpoints repair. It long been recognised as an important target for cancer therapy but inhibitors have proved elusive. As NU6027, originally developed CDK2 inhibitor, potentiated cisplatin CDK2-independent manner we postulated that it may inhibit ATR. Cellular ATR activity was determined by CHK1 phosphorylation human fibroblasts with...
Up to 50% of epithelial ovarian cancers (EOC) display defects in the homologous recombination (HR) pathway. We sought determine ramifications recombination-deficient (HRD) status on clinicopathologic features, chemotherapy response, and survival outcomes patients with EOCs. HR was determined primary cultures from ascitic fluid 50 chemotherapy-naïve by a functional RAD51 immunofluorescence assay correlated vitro sensitivity PARP inhibitor (PARPi), rucaparib. All went receive platinum-based...
BackgroundEndometrial cancer (EC) is the most common gynaecological in developed nations and its incidence rising. As a direct consequence, more women are dying from EC despite advances care improved survivorship. There lack of research activity funding, as well public awareness about EC. We sought to engage patients, carers healthcare professionals identify important unanswered questions EC.MethodologyThe priority setting methodology was by James Lind Alliance involved four key stages:...
Abstract High-grade serous ovarian carcinoma is characterised by TP53 mutation and extensive chromosome instability (CIN). Because our understanding of CIN mechanisms based largely on analysing established cell lines, we developed a workflow for generating ex vivo cultures from patient biopsies to provide models that support interrogation in cells not extensively cultured vitro. Here, describe “living biobank” cancer with replicative capacity, derived both ascites solid biopsies. Fifteen are...
Abstract The drivers of recurrence and resistance in ovarian high grade serous carcinoma remain unclear. We investigate the acquisition by collecting tumour biopsies from a cohort 276 women with relapsed BriTROC-1 study. Panel sequencing shows close concordance between diagnosis relapse, only four discordant cases. There is also very strong copy number no significant difference purity, ploidy or focal somatic alterations, even when stratified platinum sensitivity prior chemotherapy lines....
Studies in early-stage, predominantly low- and intermediate-risk endometrial cancer have demonstrated that L1 cell adhesion molecule (L1CAM) overexpression identifies patients at increased risk of recurrence, yet its prognostic significance high-risk is unclear. To evaluate this, frequency, the relationship L1CAM with established biomarker p53, we analyzed expression both markers by immunohistochemistry a pilot series 116 cancers (86 endometrioid, 30 non-endometrioid subtype) features (such...
Ki-67, a marker of cellular proliferation, is increasingly being used in pre-surgical window studies endometrial cancer as primary outcome measure. Unlike breast cancer, however, there are no guidelines standardizing its measurement and clinical relevance response biomarker undetermined. It is, therefore, imperative that Ki-67 scoring protocols optimized association with patient survival rigorously evaluated, order to be able clinically interpret the results these studies. Using...
// Fiona K. Middleton 1 , Miranda J. Patterson Claire Elstob Sarah Fordham Ashleigh Herriott Mark A. Wade Aiste McCormick Richard Edmondson Felicity E.B. May James M. Allan John R. Pollard 2 and Nicola Curtin Newcastle University, Northern Institute for Cancer Research, upon Tyne, UK Vertex Pharmaceuticals (Europe) Limited, Milton Park, Abingdon, Oxfordshire, Correspondence to: Curtin, email: Keywords : ATR, p53, DNA damage response, DNA-PKcs, synthetic lethality Received April 07, 2015...
DNA damage defects are common in ovarian cancer and can be used to stratify treatment. Although most work has focused on homologous recombination (HR), double-strand breaks repaired primarily by nonhomologous end joining (NHEJ). Defects NHEJ have been shown contribute genomic instability associated with the development of chemoresistance.
Recommendations are graded as per the Royal College of Obstetricians and Gynaecologists document, Clinical Governance Advice No. 1: Guidance for Development RCOG Green-top Guidelines, available on website at (see Supplementary Tables 1 2 below www.rcog.org.uk/rcog). Definitions certainty evidence based formal GRADE assessment within systematic reviews given in Table 3 [682GRADE Handbook.: Working Group; 2013. Available from:...