A novel spontaneous model of epithelial-mesenchymal transition (EMT) using a primary prostate cancer derived cell line demonstrating distinct stem-like characteristics

Cells acquire the invasive and migratory properties necessary for the invasion-metastasis cascade and the establishment of aggressive, metastatic disease by reactivating a latent embryonic programme: epithelial-to-mesenchymal transition (EMT). Herein, we report the development of a new, spontaneous model of EMT which involves four phenotypically distinct clones derived from a primary tumour-derived human prostate cancer cell line (OPCT-1), and its use to explore relationships between EMT and the generation of cancer stem cells (CSCs) in prostate cancer. Expression of epithelial (E-cadherin) and mesenchymal markers (vimentin, fibronectin) revealed that two of the four clones were incapable of spontaneously activating EMT, whereas the others contained large populations of EMT-derived, vimentin-positive cells having spindle-like morphology. One of the two EMT-positive clones exhibited aggressive and stem cell-like characteristics, whereas the other was non-aggressive and showed no stem cell phenotype. One of the two EMT-negative clones exhibited aggressive stem cell-like properties, whereas the other was the least aggressive of all clones. These findings demonstrate the existence of distinct, aggressive CSC-like populations in prostate cancer, but, importantly, that not all cells having a potential for EMT exhibit stem cell-like properties. This unique model can be used to further interrogate the biology of EMT in prostate cancer

The Human Phenotype Ontology in 2024: phenotypes around the world

\ua9 The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Electron microscope studies of irradiated beryllium metal.

When beryllium is irradiated by fast neutrons, helium is produced by the (n,2n) and (n,α) transmutation reactions. Electron microscopy techniques have been used to study the nucleation and distribution of helium bubbles in several different grades of beryllium, after irradiation at temperatures in the range 75 — 700ºC. The effect of post-irradiation annealing is also reported. It is shown that for similar neutron doses and irradiation temperatures, there were wide variations in helium bubble size and distribution in specimens of beryllium fabricated by different methods. The most satisfactory material was that fabricated from Pechiney powder by direct hot extrusion followed by annealing for one hour at 800ºC and air cooling, it is suggested that the helium bubbles nucleate on second phase precipitates and that the distribution of this phase is strongly affected by fabrication and heat treatment

Investigational therapies targeted to the treatment of benign prostatic hyperplasia

Introduction: The desired goals of treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) include sustained, clinically significant improvement in symptoms and quality of life and/or slowing or preventing the progression of the condition. There is a continuing interest in research for new therapies for BPH due to the high prevalence of the condition and the unmet expectations of patients and physicians from the efficacy of available therapies. Areas covered: The aim of this paper is to provide the latest data on new medical treatments for LUTS/BPH, defined as pharmacological treatments not yet commonly available and/or currently under investigation. Articles were identified by means of a computerised Google and PubMed search and a search of the trial registries. Expert opinion: Many potential targets for future drugs have been evaluated but it is obvious that there is a wide variation in the degree of mature of each therapy. Time and high-quality studies will decide which of these potential drugs will fade away without fulfilling the initial promises. At the moment, phosphodiesterase type 5 inhibitors are claiming their position in the armamentarium of BPH treatment