Recent submissions
Now showing items 2741-2760 of 4712
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Rationale and design of the POLEM trial: avelumab plus fluoropyrimidine-based chemotherapy as adjuvant treatment for stage III mismatch repair deficient or POLE exonuclease domain mutant colon cancer: a phase III randomised study.
(ELSEVIER, 2020-01-01)BACKGROUND: 10%-15% of early-stage colon cancers harbour either deficient mismatch repair (dMMR), microsatellite instability high (MSI-H) or POLE exonuclease domain mutations, and are characterised by high tumour mutational ... -
Failure-Free Survival and Radiotherapy in Patients With Newly Diagnosed Nonmetastatic Prostate Cancer: Data From Patients in the Control Arm of the STAMPEDE Trial.
(AMER MEDICAL ASSOC, 2016-03-01)IMPORTANCE: The natural history of patients with newly diagnosed high-risk nonmetastatic (M0) prostate cancer receiving hormone therapy (HT) either alone or with standard-of-care radiotherapy (RT) is not well documented. ... -
Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial.
(ELSEVIER SCIENCE INC, 2016-03-19)BACKGROUND: Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with ... -
Laser-free pelvic alignment in an online adaptive radiotherapy environment.
(2020-03)The MR-Linac (MRL) provides a novel treatment modality that enables online adaptive treatments, but also creates new challenges for patient positioning in a laser-free environment. The accuracy and duration of prostate ... -
Cryo-EM structures of the XPF-ERCC1 endonuclease reveal how DNA-junction engagement disrupts an auto-inhibited conformation.
(NATURE PUBLISHING GROUP, 2020-02-28)The structure-specific endonuclease XPF-ERCC1 participates in multiple DNA damage repair pathways including nucleotide excision repair (NER) and inter-strand crosslink repair (ICLR). How XPF-ERCC1 is catalytically activated ... -
Intraductal patient-derived xenografts of estrogen receptor α-positive breast cancer recapitulate the histopathological spectrum and metastatic potential of human lesions.
(WILEY, 2019-03-01)Estrogen receptor α-positive (ER-positive) or 'luminal' breast cancers were notoriously difficult to establish as patient-derived xenografts (PDXs). We and others recently demonstrated that the microenvironment is critical ... -
Magnetic resonance imaging sequence evaluation of an MR Linac system; early clinical experience.
(Elsevier BV, 2019-12-16)OBJECTIVES: To systematically identify the preferred magnetic resonance imaging (MRI) sequences following volunteer imaging on a 1.5 Tesla (T) MR-Linear Accelerator (MR Linac) for future protocol development. METHODS: ... -
Investigating the mehcanisms of drug resistance in gastro-intestinal cancers
(Institute of Cancer Research (University Of London), 2020-03-31)Despite many effective therapies for gastro-intestinal (GI) cancers, both primary and acquired mechanisms of resistance commonly occur. The subclonal complexity of intra-tumoural heterogeneity in these cancers further ... -
Phosphorylation-mediated interactions with TOPBP1 couple 53BP1 and 9-1-1 to control the G1 DNA damage checkpoint.
(ELIFE SCIENCES PUBLICATIONS LTD, 2019-05-28)Coordination of the cellular response to DNA damage is organised by multi-domain 'scaffold' proteins, including 53BP1 and TOPBP1, which recognise post-translational modifications such as phosphorylation, methylation and ... -
Selection and Characterization of a Nanobody Biosensor of GTP-Bound RHO Activities.
(MDPI, 2019-01-09)RHO (Ras HOmologous) GTPases are molecular switches that activate, in their state bound to Guanosine triphosphate (GTP), key signaling pathways, which involve actin cytoskeleton dynamics. Previously, we selected the nanobody ... -
Small-molecule targeting of brachyury transcription factor addiction in chordoma.
(2019-02)Chordoma is a primary bone cancer with no approved therapy 1 . The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in ... -
How RhoGEFs drive triple negative breast cancer cell invasion through the activation of YAP and TAZ
(Institute of Cancer Research (University Of London), 2020-03-31)Dynamical remodelling of the cytoskeleton is essential for triple negative breast cancer metastasis (TNBC). Cell shape is regulated by RhoGEFs which activate Rho GTPases resulting in changes in actin polymerisation, ... -
Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3.
(NATURE PORTFOLIO, 2019-06-12)Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ... -
KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe.
(NATURE PUBLISHING GROUP, 2019-06-13)Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ... -
Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer.
(AMER ASSOC CANCER RESEARCH, 2020-04-15)PURPOSE: Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at ... -
Circulating cell-free DNA: Translating prostate cancer genomics into clinical care.
(ELSEVIER, 2020-04-01)Only in the past decade tremendous advances have been made in understanding prostate cancer genomics and consequently in applying new treatment strategies. As options regarding treatments are increasing so are the challenges ... -
CALIBER: a phase II randomized feasibility trial of chemoablation with mitomycin-C vs surgical management in low-risk non-muscle-invasive bladder cancer.
(WILEY, 2020-06-01)OBJECTIVES: To evaluate the activity of intravesical mitomycin-C (MMC) to ablate recurrent low-risk non-muscle-invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for ... -
Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial.
(AMER SOC CLINICAL ONCOLOGY, 2020-02-10)PURPOSE: The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in triple-negative breast cancer (TNBC). The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and ... -
Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.
(WILEY, 2020-09-01)Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies ... -
IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche.
(2020-02-07)Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human ...