A5087609764- Advanced Breast Cancer Therapies
- Cancer Genomics and Diagnostics
- HER2/EGFR in Cancer Research
- Cancer Treatment and Pharmacology
- Breast Cancer Treatment Studies
- Molecular Biology Techniques and Applications
- Colorectal Cancer Treatments and Studies
- Monoclonal and Polyclonal Antibodies Research
- Estrogen and related hormone effects
- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Reproductive Biology and Fertility
- Peptidase Inhibition and Analysis
- Metastasis and carcinoma case studies
- Sperm and Testicular Function
- PARP inhibition in cancer therapy
- Cancer Immunotherapy and Biomarkers
- Science, Research, and Medicine
- Gastric Cancer Management and Outcomes
- Chronic Lymphocytic Leukemia Research
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Cancer-related Molecular Pathways
- Single-cell and spatial transcriptomics
- Genetic factors in colorectal cancer
Velindre Cancer Centre
2018-2024
Novartis (Ireland)
2023-2024
Velindre NHS Trust
2018-2024
Patient-Centered Outcomes Research Institute
2021
Whitchurch Hospital
2020
Royal Free London NHS Foundation Trust
2019
Guy's and St Thomas' NHS Foundation Trust
2019
Royal Marsden NHS Foundation Trust
2019
University College London Hospitals NHS Foundation Trust
2019
University Hospitals of Morecambe Bay NHS Foundation Trust
2019
Patients with pretreated estrogen receptor (ER)-positive/human epidermal growth factor 2 (HER2)-negative advanced breast cancer have poor prognosis. Elacestrant is a novel, oral selective ER degrader that demonstrated activity in early studies.
Capivasertib (AZD5363) is a potent selective oral inhibitor of all three isoforms the serine/threonine kinase AKT. The FAKTION trial investigated whether addition capivasertib to fulvestrant improved progression-free survival in patients with aromatase inhibitor-resistant advanced breast cancer.
Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple-negative breast cancer (TNBC) patients predicts high risk relapse. c-TRAK TN assessed the utility prospective ctDNA surveillance TNBC and activity pembrolizumab with detected [ctDNA positive (ctDNA+)].c-TRAK TN, a multicentre phase II trial, integrated by digital PCR, enrolled residual disease following neoadjuvant chemotherapy, or stage II/III adjuvant chemotherapy. comprised three-monthly blood sampling to 12...
Capivasertib, an AKT inhibitor, added to fulvestrant, was previously reported improve progression-free survival in women with aromatase inhibitor-resistant oestrogen receptor (ER)-positive, HER2-negative advanced breast cancer. The benefit appeared be independent of the phosphoinositide 3-kinase (PI3K)/AKT/phosphatase and tensin homologue (PTEN) pathway alteration status tumours, as ascertained using assays available at time. Here, we report updated overall results, a prespecified...
Nucleotide sequences of the homologous tetracycline resistance (tet) determinants plasmid RP1 and transposon Tn1721 have been determined. Two open reading frames divergent polarity assigned to a regulatory gene (tetR) encoding protein (tetA). The intercistronic region contains appropriate transcription signals. tetR can code for 216 araino acids (deduced mol.wt. 23,288) tetA 399 amino raol. wt. 42,205). Based on deduced acid sequence, proteins RP1/Tn1721 are 78% with that pBR322 45% TnlO. We...
Abstract Background: In patients (pts) with ER+/HER2− metastatic breast cancer (MBC) following progression on prior endocrine and CDK4/6i therapy, the EMERALD trial demonstrated significantly prolonged progression-free survival (PFS) a manageable safety profile for elacestrant versus standard of care therapy (SoC). Benefit was observed in all pts ESR1 mutant MBC (ESR1-mut). is only oral SERD monotherapy pivotal where were pretreated CDK4/6 inhibitor (CDK 4/6i). Here, we examine impact...
Using several actin isotype-specific cDNA probes, we found mRNA of two size classes, 2.1 and 1.5 kilobases (kb), in extracts polyadenylated nonpolyadenylated RNA from sexually mature CD-1 mouse testes. Although the 2.1-kb sequence was present both meiotic postmeiotic testicular cell types, it decreased manyfold late haploid cells. The 1.5-kb not detectable pachytene spermatocytes (or liver or kidney cells), but round elongating spermatids residual bodies. To differentiate between beta-...
<h3>Importance</h3> Patients with breast cancer remain at risk of relapse after adjuvant therapy. Celecoxib has shown antitumor effects in preclinical models human cancer, but clinical evidence is lacking. <h3>Objective</h3> To evaluate the role celecoxib as an addition to conventional therapy for women ERBB2 (formerly HER2)–negative primary cancer. <h3>Design, Setting, and Participants</h3> The Randomized European Trial (REACT) was a phase 3, randomized, double-blind study conducted 160...
1005 Background: The PI3K/AKT signalling pathway is frequently activated in patients (pts) with estrogen receptor (ER) positive breast cancer (ER+BC) and has been implicated endocrine therapy resistance. Capivasertib (AZD5363) a highly-selective, oral, small molecule AKT inhibitor. FAKTION trial investigated the addition of capivasertib to fulvestrant for postmenopausal women ER+ HER2 negative BC after relapse or disease progression on an aromatase inhibitor (AI). Methods: investigator-led,...
Abstract Purpose: Detection of circulating tumor DNA (ctDNA) in patients who have completed treatment for early-stage breast cancer is associated with a high risk relapse, yet the optimal assay ctDNA detection unknown. Experimental Design: The cTRAK-TN clinical trial prospectively used tumor-informed digital PCR (dPCR) assays molecular residual disease (MRD) triple-negative cancer. We compared dPCR personalized multimutation sequencing 141 from cTRAK-TN. Results: MRD was first detected by...
Mouse testis contains two size classes of actin mRNAs 2.1 and 1.5 kilobases (kb). The 2.1-kb mRNA codes for cytoplasmic beta- gamma-actin is found throughout spermatogenesis, while the 1.5-kb first detected in postmeiotic cells. Here we identify testicular encoded by as a smooth-muscle (SMGA) present its cDNA sequence. amino acid sequence deduced from was nearly identical to that chicken gizzard SMGA, with one replacement at 359, where glutamine substituted proline. nucleotide untranslated...
Interfering intracellular antibodies are valuable for biological studies as drug surrogates and potential macromolecular drugs per se. Their application is still limited because of the difficulty acquisition functional antibodies. We describe use new antibody capture procedure (IAC(3)) to facilitate direct isolation single domain fragments using four independent target molecules (LMO2, TP53, CRAF1, Hoxa9) from a set diverse libraries. Initially, these have variability in only one three...
Older patients are at higher risk of chemotherapy-induced toxicity, raising interest in less toxic anti-HER2 regimens for older persons with HER2-positive (HER2+) metastatic breast cancer (MBC).This phase II study randomized (1:1) HER2+ MBC, aged 70+ or frail 60+, to first line chemotherapy metronomic oral cyclophosphamide (M) + Trastuzumab (T) and Pertuzumab (P) TP alone. T-DM1 was offered case progression.In total, 39 41 were TPM arm respectively. Median follow-up is 54.0 months. 24-month...
Abstract Background: Endocrine therapy(ET) plus CDK4/6 inhibitor (i) is the mainstay for management of estrogenreceptor-positive (ER+)/HER2- mBC. However, most patients (pts) with ER+ mBCeventually experience disease progression, including development ESR1mutations (mESR1). Elacestrant, an oral SERD, demonstrated preclinical activity,and clinical activity in a phase 1 trial mBC, responses ptswith prior fulvestrant, CDK4/6i, and mESR1tumors (Bardia JCO 2021).. Methods: EMERALD(NCT03778931),...
Abstract Purpose The development of oestrogen resistance is a major challenge in managing hormone-sensitive metastatic breast cancer. Saracatinib (AZD0530), an oral Src kinase inhibitor, prevents animal models and reduces osteoclast activity. We aimed to evaluate the efficacy saracatinib addition aromatase inhibitors (AI) patients with hormone receptor-positive Methods This phase II multicentre double-blinded randomised trial allocated post-menopausal women AI either or placebo (1:1 ratio)....
Because a restricted repertoire of T-cell receptor (TCR) Vβp gene expression has been reported in other autoimmune diseases, the possibility similarly Vα by infiltrates NOD mouse islets was examined. With isolated from 4- to 12-wk-old mice, prospective polymerase chain reaction analysis with 18 Vβ-specific oligonucleotide primers performed on noncloned and unexpanded islet-infiltrating T cells. The methodology used permitted detection minimum 50 In contrast TCR Vβ usage for even youngest...
Abstract Background Detection of circulating tumour DNA (ctDNA) in patients (pts) who have completed treatment for early-stage triple negative breast cancer (TNBC) is associated with a very high risk future relapse. Identifiying those at subsequent relapse may allow tailoring further therapy to delay or prevent recurrence. The c-TRAK TN trial assessed the utility prospective ctDNA surveillance pts treated TNBC and activity pembrolizumab (P) detected.. Methods TN, multi-centre phase II...
Abstract Purpose: Neratinib plus capecitabine (N+C) demonstrated significant progression-free survival (PFS) benefit in NALA (NCT01808573), a randomized phase III trial comparing N+C with lapatinib + (L+C) 621 patients HER2-positive (HER2+) metastatic breast cancer (MBC) who had received ≥2 prior HER2-directed regimens the setting. We evaluated correlations between exploratory biomarkers and PFS. Patients Methods: Somatic mutations were by next-generation sequencing on primary or samples....
Introduction: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis for relapsed/refractory disease. The WHO classification NK and includes 39 entries; the 3 most common subtypes in US are PTCL-NOS (not otherwise specified), angioimmunoblastic (AITL), anaplastic large-cell (ALCL). Except brentuximab vedotin CD30-positive disease, agents were generally approved based on overall response rates (ORR) less than 30%. PRIMO Trial (NCT03372057;...