Publications by authors named "Ian Reddin"
Two APOBEC DNA cytosine deaminase enzymes, APOBEC3A and APOBEC3B, generate somatic mutations in cancer, thereby driving tumour development and drug resistance. Here, we used single-cell RNA sequencing to study APOBEC3A and APOBEC3B expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas APOBEC3B is expressed in keratinocytes entering mitosis, we show that APOBEC3A expression is confined largely to terminally differentiating cells and requires grainyhead-like transcription factor 3 (GRHL3).
View Article and Find Full Text PDFEpigenetic profiling of prostate cancer reveals potential prognostic signatures.
J Cancer Res Clin Oncol
August 2024
Purpose: While epigenetic profiling discovered biomarkers in several tumor entities, its application in prostate cancer is still limited. We explored DNA methylation-based deconvolution of benign and malignant prostate tissue for biomarker discovery and the potential of radiomics as a non-invasive surrogate.
Methods: We retrospectively included 30 patients (63 [58-79] years) with prostate cancer (PCa) who had a multiparametric MRI of the prostate before radical prostatectomy between 2014 and 2019.
The congenital condition gastroschisis is associated with delayed villous development and placental malperfusion, suggesting placental involvement. This study uses RNA sequencing to compare the placental transcriptome in pregnancies with and without gastroschisis. 180 coding genes were differentially expressed, mapping to multiple gene ontology pathways.
View Article and Find Full Text PDFTwo APOBEC (apolipoprotein-B mRNA editing enzyme catalytic polypeptide-like) DNA cytosine deaminase enzymes (APOBEC3A and APOBEC3B) generate somatic mutations in cancer, driving tumour development and drug resistance. Here we used single cell RNA sequencing to study and expression in healthy and malignant mucosal epithelia, validating key observations with immunohistochemistry, spatial transcriptomics and functional experiments. Whereas is expressed in keratinocytes entering mitosis, we show that expression is confined largely to terminally differentiating cells and requires Grainyhead-like transcription factor 3 (GRHL3).
View Article and Find Full Text PDFBackground: Rhabdomyosarcomas (RMS) are predominantly paediatric sarcomas thought to originate from muscle precursor cells due to impaired myogenic differentiation. Despite intensive treatment, 5-year survival for patients with advanced disease remains low (< 30%), highlighting a need for novel therapies to improve outcomes. Differentiation therapeutics are agents that induce differentiation of cancer cells from malignant to benign.
View Article and Find Full Text PDFArticle Synopsis
- - Cancer drug development faces challenges due to high clinical attrition rates, largely attributed to unreliable preclinical models and variability in experimental results.
- - An analysis of the extensive NCI60 cancer cell line data revealed significant variability in growth inhibition (GI50) outcomes, even when standard protocols were followed, suggesting that this inconsistency is a fundamental issue in anti-cancer testing.
- - Recognizing this variability is crucial for interpreting data realistically and highlights the need for further research into diverse model systems to potentially enhance data reliability in cancer drug development.
This review aimed to examine the relationship between TP53 mutational status, as determined by genomic sequencing, and survival in squamous cell carcinoma of the head and neck. The databases Medline, Embase, Web of Science (core collection), Scopus and Cochrane Library were searched from inception to April 2021 for studies assessing P53 status and survival. Qualitative analysis was carried out using the REMARK criteria.
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- HPV-associated cervical cancer is a major cause of cancer deaths in women, and this study analyzed 643 cases of cervical squamous cell carcinomas (CSCC) from the USA, Europe, and Sub-Saharan Africa.
- The researchers identified two distinct CSCC subtypes, C1 and C2, which have different prognoses, but the differences are not solely related to the HPV types (16 and 18) commonly found in these tumors.
- C2 tumors, accounting for about 20% of CSCCs, exhibit unique genomic changes and immune characteristics, leading to shorter survival rates, highlighting their significance for future treatment approaches.
Article Synopsis
- Survivin is a drug target, and the drug candidate YM155 has shown promise for treating high-risk neuroblastoma, but some cancer cells can develop resistance to it.
- In a study of YM155-adapted UKF-NB-3 sublines, researchers found that increased ABCB1 levels and decreased SLC35F2 levels were linked to YM155 resistance, but these indicators did not predict sensitivity to YM155 in untreated cells.
- The resistant sublines displayed high heterogeneity and varied responses to other anti-cancer drugs, suggesting that cancer treatment needs to be personalized and that monitoring cell evolution and resistance indicators is essential.
Motivation: Ebola viruses are not pathogenic but can be adapted to replicate and cause disease in rodents. Here, we used a structural bioinformatics approach to analyze the mutations associated with Ebola virus adaptation to rodents to elucidate the determinants of host-specific Ebola virus pathogenicity.
Results: We identified 33 different mutations associated with Ebola virus adaptation to rodents in the proteins GP, NP, L, VP24 and VP35.