ATLA 43.6, December 2015

//ATLA 43.6, December 2015

IIVS News & Views

Institute for In Vitro Sciences staff

IIVS Training in China
IIVS Practical Methods in In Vitro Toxicology Workshop
IIVS to Host April 2016 Workshop — In Vitro Exposure Systems and Dosimetry Assessment Tools for Inhaled Tobacco Products
EPA Updates its Policy on an Important ‘Six-pack’ Endpoint Following Collaboration with IIVS and Industry

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2017-01-09T06:02:34+00:00 Tags: , |

SEARCHBreast Workshop Proceedings: 3D Modelling of Breast Cancer

Bethny Morrissey, Karen Blyth, Phil Carter, Claude Chelala, Ingunn Holen, Louise Jones and Valerie Speirs

SEARCHBreast, a UK initiative supported by the NC3Rs, organised a workshop entitled 3D Modelling of Breast Cancer. The workshop focused on providing researchers with solutions to overcome some of the perceived barriers to working with human-derived tumour cells, cell lines and tissues, namely: a) the limited access to human-derived material; and b) the difficulty in working with these samples. The workshop presentations provided constructive advice and information on how to best prepare human cells or tissues for further downstream applications. Techniques in developing primary cultures from patient samples, and considerations when preserving tissue slices, were discussed. A common theme throughout the workshop was the importance of ensuring that the cells are grown in conditions as similar to the in vivo microenvironment as possible. Comparisons of the advantages of several in vitro options, such as primary cell cultures, cell line cultures, explants or tissue slices, suggest that all offer great potential applications for breast cancer research, and highlight that it need not be a case of choosing one over the other. The workshop also offered cutting-edge examples of on-chip technologies and 3-D tumour modelling by using virtual pathology, which can contribute to clinically relevant studies and provide insights into breast cancer metastatic mechanisms.

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3-D Tissue Modelling and Virtual Pathology as New Approaches to Study Ductal Carcinoma In Situ

Mary E. Booth, Claire E. Nash, Nicholas P. Roberts, Derek R. Magee, Darren Treanor,
Andrew M. Hanby and Valerie Speirs

Widespread screening mammography programmes mean that ductal carcinoma in situ (DCIS), a pre-invasive breast lesion, is now more frequently diagnosed. However, not all diagnosed DCIS lesions progress to invasive breast cancer, which presents a dilemma for clinicians. As such, there is much interest in studying DCIS in the laboratory, in order to help understand more about its biology and determine the characteristics of those that progress to invasion. Greater knowledge would lead to targeted and better DCIS treatment. Here, we outline some of the models available to study DCIS, with a particular focus on animal-free systems.

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2017-01-09T06:02:35+00:00 Tags: , , , |

Conditions and Possible Mechanisms of VCD-induced Ovarian Failure

Wei Liu, Ling-Yan Wang, Xiao-Xue Xing and Guan-Wei Fan

Perimenopause is an important period in women’s lives, in which they experience a series of physiological changes. Current animal models of perimenopause fail to adequately replicate this particular stage in female life, while current in vitro models are too simplistic and cannot account for systemic effects. Neither the naturally-ageing animal model, nor the ovariectomised animal model, mimic the natural transitional process that is the menopause. In vivo and in vitro studies have confirmed that the occupational chemical, 4-vinylcyclohexene diepoxide (VCD), can cause selective destruction of the ovarian primordial and primary follicles of rats and mice by accelerating the apoptotic process, which successfully mimics the perimenopausal state in women. However, it is the in vivo VCD-induced rodent perimenopausal models that are currently the most widely used in research, rather than any of the available in vitro models. Studies on the mechanisms involved have found that VCD induces ovotoxicity via interference with the c-kit/kit ligand and apoptotic signalling pathways, among others. Overall, the VCD-induced perimenopausal animal models have provided some insight into female perimenopause, but they are far from ideal models of the human situation.

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Predicting Human Drug Toxicity and Safety via Animal Tests: Can Any One Species Predict Drug Toxicity in Any Other, and Do Monkeys Help?

Jarrod Bailey, Michelle Thew and Michael Balls

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for different classes of drugs. Here, we present further data from analyses of other species pairs, including nonhuman primates (NHPs), which support our previous conclusions, and also show in particular that test results inferring an absence of toxicity in one species provide no evidential weight with regard to toxicity in any other species, even when data from NHPs and humans are compared. Our results for species including humans, NHPs, dogs, mice, rabbits, and rats, have major implications for the value of animal tests in predicting human toxicity, and demand that human-focused alternative methods are adopted in their place as a matter of urgency.
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The Björn Ekwall Memorial Award 2015

Introduction by Ada Kolman & lecture text by Michael Balls

A personal, and therefore unavoidably biased, review is given, of the significance of the contributions made by selected Scandinavian individuals, organisations and events, to the development of in vitro toxicology procedures as potential replacements for toxicity tests in laboratory animals. In addition to their wider significance, these contributions had a profound effect on whatever contributions I have been able to make, myself. Nevertheless, while there has been much progress in the last 35 years or so, and many lessons have been learned, there is still much to be done, especially as animal tests remain entrenched as the preferred methods which set the gold standards and make regulators feel comfortable. Many of the clues to dealing with the questions and concerns which plague hazard prediction and risk assessment have long been available, but they have been ignored, largely for reasons which have little to do with the science of toxicology and the need to maintain the highest scientific standards. I have little doubt that Björn Ekwall, whose memory I feel privileged to honour, would have agreed with that last statement.
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On the Safety of E-cigarettes: “I can resist anything except temptation”

Robert D. Combes and Michael Balls

Strategic policy decisions are being made about e-cigarettes, based on the plausibility of their greater safety, rather than on essential scientific evidence which would permit a proper risk assessment. If e-cigarettes are really ‘safer’, then their use should be recommended, but only after an intelligent analysis of their risk to human health, based on integrated in silico, in vitro and clinical studies for both scientific and logistical reasons.
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