Guidelines for cellular and molecular pathology content in clinical trial protocols: the SPIRIT-Path extension.

The 2013 SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) Statement provides evidence-based recommendations for the minimum content to be included in a clinical trial protocol. Assessment of biospecimens is often required for trial eligibility or as part of an outcome evaluation, and precision molecular approaches are increasingly used in trial design. However, cellular and molecular pathology practices within trials have not been codified or formalised.

The important role of the histopathologist in clinical trials: challenges and approaches to tackle them.

High-quality histopathology is essential for the success of clinical trials. Histopathologists have a detailed understanding of tumour biology and mechanisms of disease, as well as practical knowledge of optimal tissue handling and logistical service requirements for study delivery, such as biomarker evaluation, tissue acquisition and turnaround times. As such, histopathologist input is essential throughout every stage of research and clinical trials, from concept development and study design to trial delivery, analysis and dissemination of results.

Improving attribution of adverse events in oncology clinical trials.

Attribution of adverse events (AEs) is critical to oncology drug development and the regulatory process. However, processes for determining the causality of AEs are often sub-optimal, unreliable, and inefficient. Thus, we conducted a toxicity-attribution workshop in Silver Springs MD to develop guidance for improving attribution of AEs in oncology clinical trials.

Incorporating the patient experience into regulatory decision making in the USA, Europe, and Canada.

The clinical development of cancer therapeutics is a global undertaking, and incorporation of the patient experience into the clinical decision-making process is of increasing interest to the international regulatory and health policy community. Disease and treatment-related symptoms and their effect on patient function and health-related quality of life are important outcomes to consider. The identification of methods to scientifically assess, analyse, interpret, and present these clinical outcomes requires sustained international collaboration by multiple stakeholders including patients, clinicians, scientists, and policy makers.

To die or not to die: how does p53 decide?

p53 is frequently mutated in cancer and as a result is one of the most intensely studied tumour suppressors. Analysis of the primitive forms of p53 found in Caenorhabditis elegans and Drosophila, alongside studies using transgenic mouse models, indicate that the induction of apoptosis is both the most conserved function of p53 and vital for tumour suppression. p53-mediated apoptosis occurs through a combination of mechanisms which include pathways that are both dependent and independent of alterations in gene expression.

iASPP oncoprotein is a key inhibitor of p53 conserved from worm to human.

We have previously shown that ASPP1 and ASPP2 are specific activators of p53; one mechanism by which wild-type p53 is tolerated in human breast carcinomas is through loss of ASPP activity. We have further shown that 53BP2, which corresponds to a C-terminal fragment of ASPP2, acts as a dominant negative inhibitor of p53 (ref. 1).

Additive intraocular pressure lowering effect of various medications with latanoprost.

Purpose: To determine the additive intraocular pressure reduction of various topical glaucoma agents used adjunctively with latanoprost.

Design: Retrospective interventional case series.

Methods: Retrospective evaluation of 73 eyes of 73 patients with glaucoma and inadequate intraocular pressure control on latanoprost alone.

Novel function of the cyclin A binding site of E2F in regulating p53-induced apoptosis in response to DNA damage.

We demonstrate here that the E2F1 induced by DNA damage can bind to and promote the apoptotic function of p53 via the cyclin A binding site of E2F1. This function of E2F1 does not require its DP-1 binding, DNA binding, or transcriptional activity and is independent of mdm2. All the cyclin A binding E2F family members can interact and cooperate with p53 to induce apoptosis.