Margaret A. Knowles
A5064065033- Bladder and Urothelial Cancer Treatments
- Epigenetics and DNA Methylation
- Fibroblast Growth Factor Research
- Urinary and Genital Oncology Studies
- Renal cell carcinoma treatment
- Cancer Genomics and Diagnostics
- Ferroptosis and cancer prognosis
- Cancer, Hypoxia, and Metabolism
- RNA modifications and cancer
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Cancer-related Molecular Pathways
- Metastasis and carcinoma case studies
- DNA Repair Mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Genetic and Kidney Cyst Diseases
- Esophageal Cancer Research and Treatment
- Eosinophilic Disorders and Syndromes
- Prostate Cancer Treatment and Research
- Urological Disorders and Treatments
- Renal and related cancers
- Glutathione Transferases and Polymorphisms
- Cancer-related gene regulation
- Kruppel-like factors research
- Tissue Engineering and Regenerative Medicine
University of North Carolina at Chapel Hill
1985-2025
St James's University Hospital
2015-2024
University of Leeds
2015-2024
Cancer Research UK
2005-2023
Cancer Research And Biostatistics
2023
Institute of Molecular Medicine
2014-2023
Bristol Royal Infirmary
2023
Kenya Medical Training College
2023
British Association of Dermatologists
2023
Policlinico Casilino
2020
Abstract Protein kinases are frequently mutated in human cancer and inhibitors of mutant protein have proven to be effective anticancer drugs. We screened the coding sequences 518 (∼1.3 Mb DNA per sample) for somatic mutations 26 primary lung neoplasms seven cell lines. One hundred eighty-eight were detected 141 genes. Of these, 35 synonymous (silent) changes. This result indicates that most 188 “passenger” not causally implicated oncogenesis. However, an excess ∼40 nonsynonymous...
FGF receptor 3 (FGFR3) is activated by mutation or over-expression in many bladder cancers. Here, we identify an additional mechanism of activation via chromosomal re-arrangement to generate constitutively fusion genes. FGFR3-transforming acid coiled coil (TACC3) fusions resulting from 4p16.3 re-arrangements and a t(4;7) that generates FGFR3-BAI1-associated protein 2-like 1 (BAIAP2L1) were identified 4 43 tumour cell lines 2 32 selected tissue samples including the which one was derived....
Systematic sequence profiling of the Glioblastoma Multiforme (GBM) genome has recently led to identification somatic mutations in isocitrate dehydrogenase 1 (IDH1) gene. Interestingly, only evolutionarily conserved residue R132 located substrate binding site IDH1 was found mutated GBM. At present, occurrence and relevance p.R132 (IDH1(R132)) variants tumors other than GBMs is largely unknown. We searched for at position gene a panel 672 tumor samples. These included high-grade glioma,...
FGFR3 is frequently activated by mutation in urothelial carcinoma (UC) and represents a potential target for therapy. In multiple myeloma, both over-expression of contribute to tumour development. To define the population UC patients who may benefit from FGFR-targeted therapy, we assessed receptor primary UCs new patients. Manual or laser capture microdissection was used isolate pure cell populations. Where present, non-invasive invasive components same section were microdissected. A screen...
Urothelial carcinoma of the bladder (UCC) is a common disease that arises by at least two different molecular pathways. The biology UCC incompletely understood, making management this difficult. Recent evidence implicates regulatory role for microRNA in cancer. We hypothesized altered expression contributes to carcinogenesis. To test hypothesis, we examined 322 microRNAs and their processing machinery 78 normal malignant urothelial samples using real-time rtPCR. Genes targeted differentially...
Abstract The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed NMIBC ( n = 834). Transcriptomic identifies four classes (1, 2a, 2b and 3) reflecting tumor biology disease aggressiveness. Both transcriptome-based subtyping the level chromosomal instability provide independent prognostic value beyond established...
Molecular recognition reagents are key tools for understanding biological processes and used universally by scientists to study protein expression, localisation interactions. Antibodies remain the most widely of such many show excellent performance, although some poorly characterised or have stability batch variability issues, supporting use alternative binding proteins as complementary applications. Here we report on Affimer research reagents. We selected 12 diverse molecular targets...
Genetic and epigenetic changes in the von Hippel-Lindau (VHL) tumor suppressor gene are common sporadic conventional renal cell carcinoma (cRCC). Further insight into clinical significance of these may lead to increased biological understanding identification subgroups patients differing prognostically or who benefit from specific targeted treatments. We have comprehensively examined VHL status tissue samples 115 undergoing nephrectomy, including 96 with cRCC. In cRCC, loss heterozygosity...
Abstract Renal cell carcinoma (RCC) is the tenth most common cancer although incidence increasing. The main clinical problems stem from relatively late presentation of many patients due to often asymptomatic nature illness, and relative insensitivity metastatic disease conventional chemotherapy radiotherapy. Despite increasing knowledge some genetic changes underlying sporadic renal such as those involving Von Hippel Lindau (VHL) gene, pathophysiological are ill‐defined there remains a need...
Abstract Purpose: The phosphatidylinositol 3-kinase (PI3K) pathway can be activated by alterations affecting several components. For rational application of targeted therapies, detailed understanding tumor biology and approaches to predict efficacy in individual tumors are required. Our aim was assess the frequency distribution bladder cancer. Experimental Design: We examined components (PIK3CA, PTEN, TSC1, RHEB, LKB1) putative upstream regulators (FGFR3 RAS genes) for mutation, allelic...
The histiocytoses are a heterogeneous group of disorders characterised by an excessive number histiocytes. In most cases the pathophysiology is unclear and treatment nonspecific. Faisalabad histiocytosis (FHC) (MIM 602782) has been classed as autosomal recessively inherited form with similarities to Rosai-Dorfman disease (RDD) (also known sinus massive lymphadenopathy (SHML)). To elucidate molecular basis FHC, we performed autozygosity mapping studies in large consanguineous family...
Abstract Purpose: Clinically useful molecular markers predicting the clinical course of patients diagnosed with non–muscle-invasive bladder cancer are needed to improve treatment outcome. Here, we validated four previously reported gene expression signatures for diagnosis disease stage and carcinoma in situ (CIS) recurrence progression. Experimental Design: We analyzed tumors from 404 hospitals Denmark, Sweden, England, Spain, France using custom microarrays. Molecular classifications were...