Multiple initiatives have attempted to define and recommend the annotation of images with metadata. However, proper documentation of complex and evolving projects is a difficult task, and the variety of storage methods—electronic labnotebooks, metadata servers, repositories and manuscripts—along with data from different time points of a given project leads to either redundancy in annotation or omissions. In this Commentary, we discuss how to tackle this problem, taking inspiration from space communication which uses error-correction protocols based on redundancy for data transmission.
View Article and Find Full Text PDFPositron emission tomography (PET) has transformed medical imaging, and while first developed and applied to the human setting, it has found widespread application at the preclinical level over the past two decades. Its strength is that it offers noninvasive 3D tomographic imaging in a quantitative manner at very high sensitivity. Paired with the right molecular probes, invaluable insights into physiology and pathophysiology have been accessible and therapeutic development has been enhanced through preclinical PET imaging.
View Article and Find Full Text PDFIntroduction: The chemokine receptor CXCR4 has been shown to be over-expressed in multiple types of cancer and is usually associated with aggressive phenotypes and poor prognosis. Successfully targeting and imaging the expression level of this receptor in tumours could inform treatment selection and facilitate patient stratification.
Methods: Known conjugates of AMD3100 that are specific to CXCR4 have been radiolabelled with gallium-68 and evaluated in naïve and tumour-bearing mice.
Objective: Neoadjuvant chemoradiotherapy (neo-CRT) prior to surgery is the standard of care for oesophageal adenocarcinoma (OAC) patients. Unfortunately, most patients fail to respond to treatment. MiR-187 was previously shown to be downregulated in neo-CRT non-responders, whist miR-187 overexpression enhanced radiosensitivity and upregulated .
View Article and Find Full Text PDFHistone deacetylase 6 (HDAC6) is a multifunctional cytoplasmic enzyme involved in diverse cellular processes such as intracellular transport and protein quality control. Inhibition of HDAC6 can alleviate defects in cell and rodent models of certain diseases, particularly neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. However, while HDAC6 represents a potentially powerful therapeutic target, development of effective brain-penetrant HDAC6 inhibitors remains challenging.
View Article and Find Full Text PDFBackground: Many patients diagnosed with oesophageal adenocarcinoma (OAC) present with advanced disease and approximately half present with metastatic disease. Patients with localised disease, who are managed with curative intent, frequently undergo neoadjuvant chemoradiotherapy. Unfortunately, ~ 70% of patients have little or no response to chemoradiotherapy.
View Article and Find Full Text PDFExpression of the chemokine receptor chemokine C-X-C motif receptor 4 (CXCR4) plays an important role in cancer metastasis, in autoimmune diseases, and during stem cell-based repair processes after stroke and myocardial infarction. Previously reported PET imaging agents targeting CXCR4 suffer from either high nonspecific uptake or bind only to the human form of the receptor. The objective of this study was to develop a high-stability Cu-labeled small-molecule PET agent for imaging both human and murine CXCR4 chemokine receptors.
View Article and Find Full Text PDFSignificant improvements in radiotherapy are likely to come from biological rather than technical optimization, for example increasing tumour radiosensitivity via combination with targeted therapies. Such paradigms must first be evaluated in preclinical models for efficacy, and recent advances in small animal radiotherapy research platforms allow advanced irradiation protocols, similar to those used clinically, to be carried out in orthotopic models. Dose assessment in such systems is complex however, and a lack of established tools and methodologies for traceable and accurate dosimetry is currently limiting the capabilities of such platforms and slowing the clinical uptake of new approaches.
View Article and Find Full Text PDFReaction of 5,11,17,23-tetra-tert-butyl-dihydroxy-26,28-bis(2-pentoxy)calix[4]arene (L(OH)2(Opentyl)2) with [TiCl4] afforded the dichlorotitanoacalix[4]arene complex [TiCl2L(O)2(Opentyl)2] (1) in good yield. Hydrolysis of 1 led to the isolation of the complex {[TiL(O)3(Opentyl)]2(μ-OH)(μ-Cl)} (2). Reaction of 5,11,17,23,29,35,41,47-p-tert-butyl-49,50,51,52,53,54,55,56-octapropoxycalix[8]arene (L'(Opropyl)8) with [TiCl4] in refluxing toluene afforded, following work-up, a 35 : 65 mixture (3) of the complex [Ti(NCMe)Cl]2[TiCl(μ-O)]2L' and the silicone grease derived complex [Ti(NCMe)Cl]2[Ti(μ-O)]2[OSi(CH3)2OSi(CH3)2O]L' in which the grease replaces two chloride ligands.
View Article and Find Full Text PDFSolid tumors with disorganized, insufficient blood supply contain hypoxic cells that are resistant to radiotherapy and chemotherapy. Drug resistance, an obstacle to curative treatment of solid tumors, can occur via suppression of apoptosis, a process controlled by pro- and antiapoptotic members of the Bcl-2 protein family. Oxygen deprivation of human colon cancer cells in vitro provoked decreased mRNA and protein levels of proapoptotic Bid and Bad.
View Article and Find Full Text PDF