Anke Nijhuis
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View article: RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination
RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination Open
The combination of PARP and NAMPT inhibitors (PARPi/NAMPTi) has been explored for the treatment of triple-negative breast cancer, Ewing sarcoma and high-grade serous carcinoma (HGSC). However, dose limiting toxicity has hampered NAMPTi in …
View article: Exploiting the polypharmacology of alectinib for synergistic RNA splicing disruption with RBM39 degraders
Exploiting the polypharmacology of alectinib for synergistic RNA splicing disruption with RBM39 degraders Open
Precise control of pre-mRNA splicing is critical for transcriptome integrity, and its disruption is increasingly recognised as a vulnerability in cancer. Here, we identify a functional interplay between two key splicing regulators, RBM39 a…
View article: RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination
RAS/PI3K pathway mutations sensitise epithelial ovarian cancer cells to a PARP/NAMPT inhibitor combination Open
The combination of PARP and NAMPT inhibitors (PARPi/NAMPTi) has been explored for the treatment of TNBC, Ewing Sarcoma and high grade serous carcinoma (HGSC). However, dose limiting toxicity has hampered NAMPTi in clinical trials. To maxim…
View article: Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn’s Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets
Epigenetic and Metabolic Reprogramming of Fibroblasts in Crohn’s Disease Strictures Reveals Histone Deacetylases as Therapeutic Targets Open
Background and Aims No effective therapeutic intervention exists for intestinal fibrosis in Crohn’s disease [CD]. We characterized fibroblast subtypes, epigenetic and metabolic changes, and signalling pathways in CD fibrosis to inform futu…
View article: Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma Open
Ovarian high-grade serous carcinoma (HGSC) is the most common subtype of ovarian cancer with limited therapeutic options and a poor prognosis. In recent years, poly-ADP ribose polymerase (PARP) inhibitors have demonstrated significant clin…
View article: Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma
Pharmacological depletion of RNA splicing factor RBM39 by indisulam synergizes with PARP inhibitors in high-grade serous ovarian carcinoma Open
Ovarian high-grade serous carcinoma (HGSC) is the most common and lethal subtype of ovarian cancer with limited therapeutic options. In recent years, PARP inhibitors have demonstrated significant clinical benefits, especially in patients w…
View article: Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease
Small-molecule Wnt inhibitors are a potential novel therapy for intestinal fibrosis in Crohns disease Open
Intestinal fibrosis and stricture formation is an aggressive complication of Crohns disease (CD), linked to increased morbidity and costs. The present study investigates the contribution of Wingless-Int-1 (Wnt) signalling to intestinal fib…
View article: Indisulam targets RNA splicing and metabolism to serve as a novel therapeutic strategy for high-risk neuroblastoma
Indisulam targets RNA splicing and metabolism to serve as a novel therapeutic strategy for high-risk neuroblastoma Open
Neuroblastoma is the most common solid tumour in childhood and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be particularly sensi…
View article: Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells
Lactic acidosis induces resistance to the pan-Akt inhibitor uprosertib in colon cancer cells Open
Background Akt signalling regulates glycolysis and drives the Warburg effect in cancer, thus decreased glucose utilisation is a pharmacodynamic marker of Akt inhibition. However, cancer cells can utilise alternative nutrients to glucose fo…
View article: DOP20 Drugs that modulate histone acetylation disrupt TGF-β-signalling and reduce collagen I expression in models of stricturing Crohn’s disease
DOP20 Drugs that modulate histone acetylation disrupt TGF-β-signalling and reduce collagen I expression in models of stricturing Crohn’s disease Open
Stricturing Crohn’s disease (SCD) is associated with excess deposition of extracellular collagen, is not reversed by current medical therapies, and is a frequent indication for surgery. Acetylation of histone proteins is an important epige…
View article: P035 Pharmacological inhibition of the canonical WNT signalling pathway represents a potential novel therapy for fibrosis in Crohn’s disease
P035 Pharmacological inhibition of the canonical WNT signalling pathway represents a potential novel therapy for fibrosis in Crohn’s disease Open
Intestinal fibrosis and subsequent stricturing does not respond to current therapies and is the main indication for surgery in Crohn’s disease (CD). Complete understanding of the underlying molecular mechanisms of fibrosis is required to u…
View article: Epithelial down‐regulation of the miR‐200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition
Epithelial down‐regulation of the miR‐200 family in fibrostenosing Crohn's disease is associated with features of epithelial to mesenchymal transition Open
Intestinal mesenchymal cells deposit extracellular matrix in fibrotic Crohn's disease (CD). The contribution of epithelial to mesenchymal transition (EMT) to the mesenchymal cell pool in CD fibrosis remains obscure. The miR‐200 family regu…
View article: P002 Epithelial to mesenchymal transition is a hallmark of fibrostenosing Crohn’s disease and is associated with down regulation of the miR-200 family
P002 Epithelial to mesenchymal transition is a hallmark of fibrostenosing Crohn’s disease and is associated with down regulation of the miR-200 family Open
Intestinal mesenchymal cells are responsible for extracellular matrix deposition leading to fibrosis in Crohn’s disease (CD). Epithelial to mesenchymal transition (EMT) contributes to renal fibrosis1 but the role in intestinal fibrosis rem…
View article: GPER mediates differential effects of estrogen on colon cancer cell proliferation and migration under normoxic and hypoxic conditions
GPER mediates differential effects of estrogen on colon cancer cell proliferation and migration under normoxic and hypoxic conditions Open
The estrogen receptor ERβ is the predominant ER subtype expressed in normal well-differentiated colonic epithelium. However, ERβ expression is lost under the hypoxic microenvironment as colorectal cancer (CRC) malignancy progresses. This r…
View article: Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance
Remodelling of microRNAs in colorectal cancer by hypoxia alters metabolism profiles and 5-fluorouracil resistance Open
AN, HT and AP are Constance Travis post-graduate
\nfellows. NS is a Barts and The London post-doctoral fellow. SMD is a Bowel & Cancer
\nResearch post-doctoral fellow. TS is supported by a Grant-in-Aid for scientific research on
\nInnovati…
View article: Role of Reactive Oxygen Species in the Abrogation of Oxaliplatin Activity by Cetuximab in Colorectal Cancer
Role of Reactive Oxygen Species in the Abrogation of Oxaliplatin Activity by Cetuximab in Colorectal Cancer Open
Inhibition of STAT1 and DUOX2-mediated ROS generation by cetuximab impairs p38-dependent apoptosis by oxaliplatin in preclinical models and may contribute to reduced efficacy in clinical settings. Understanding the rationale for unexpected…
View article: Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohnʼs Disease Phenotype
Low Serum Levels of MicroRNA-19 Are Associated with a Stricturing Crohnʼs Disease Phenotype Open
These data identify miR-19-3p as a potential circulating marker of stricturing CD. Our data show that microRNAs have utility as noninvasive biomarkers of stricturing CD. Further longitudinal studies are required to determine the prognostic…