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Paczkowski, M.

Publications and source records attributed to Paczkowski, M..

2 recordsLinked to original sources

An innovative non-invasive technique for subcutaneous tumour measurements

In oncological drug development, animal studies continue to play a central role in which the volume of subcutaneous tumours is monitored to assess the efficacy of new drugs. Tumour volume is currently estimated by measuring length and width with callipers and then estimating the volume of the tumour as if it were a regular spheroid. However, this method is subjective, insufficiently traceable, and is subject to error in the accuracy of volume estimates as tumours frequently are irregular.\n\nThis paper explores the extent of inconsistencies in calliper measurements by conducting a statistical review of a large dataset consisting of 2,500 tumour volume measurements from 1,600 mice by multiple operators across 6 mouse strains and 20 tumour models. We also explore the impact of six different tumour morphologies on volume estimation and the detection of treatment effects using a computational tumour growth model. Finally, we propose an alternative method to callipers for estimating volume - BioVolume, a 3D scanning technique. BioVolume simultaneously captures both stereo RGB (Red, Green and Blue) images from different light sources and infrared thermal images of the tumour. It detects the tumour region automatically and estimates the tumour volume in under a second. BioVolume has been tested on a dataset of 297 scans from over 120 mice collected by four different operators.\n\nThis work demonstrates that it is possible to record tumour measurements in a rapid, minimally invasive, morphology-independent way, and with less human-bias compared to callipers, whilst also improving data traceability. Furthermore, the images collected by BioVolume may be useful, for example, as a source of biomarkers for animal welfare and secondary drug toxicity / efficacy.

cancer biology

Radiation resistant cancer cells enhance the survival and resistance of sensitive cells in prostate spheroids

Intratumoural heterogeneity contributes to local tumour recurrence and variable responses to radiotherapy in prostate cancer. Despite the multiclonal nature of the disease, tumour control probability for conventional treatment plans is modelled on the assumption that tumour cells in the target region respond identically and independently. Here, using tumour cell subpopulations with different radiation sensitivities from prostate tumour cell lines, we show that radiation resistant cells enhance the survival and radiation resistance of radio-sensitive cells in spheroids but not in monolayer culture. Mathematical modelling indicates that these phenotypic changes result from both competitive and antagonistic cellular interactions in spheroids. Interactions mediated by oxygen constraints define the spatial localisation of the cell populations in spheroids and in xenografts, while those mediated by paracrine signals further modify the microenvironment. Our results show new mechanisms of radiotherapy resistance mediated by cellular interactions and by the microenvironment.

cancer biology