Biology subjects

Bunce, E. V.

Publications and source records attributed to Bunce, E. V..

4 recordsLinked to original sources

bioRxiv2025

Unravelling the in vivo traits of vasculogenic mimicry

Vasculogenic mimicry (VM) describes the ability of cancer cells to acquire endothelial properties and form vessel-like channels that facilitate tumour blood supply. While the molecular drivers of VM have been well-explored in cell cultures and biopsies, an in vivo description remains elusive. Here, we used graph theory to define VM biomarkers and elucidate the spatiotemporal dynamics of VM using in vitro and in vivo breast cancer models with and without anti-angiogenic treatment. Optical microscopy was used to assess pseudo-vascular networks in vitro while photoacoustic imaging across scales was applied in vivo to identify and locate haemoglobin contrast-derived blood vessel morphology and functionality. VM was associated with greater oxygenation heterogeneity and poorer anti-angiogenic response, reflected as stable meshed networks in vitro and blood-containing circular structures in vivo. We demonstrate for the first time a multi-scale approach bridging the in vitro-in vivo translational gap to assess anti-vascular treatment resistance and the therapeutic potential in vasculogenic mimicry-rich tumours, exploring novel avenues in preclinical drug screening and systemic drug delivery.

cancer biology↗

bioRxiv2025

Early Radiation Therapy Response Assessment using Multi-scale Photoacoustic Imaging

There is a critical unmet clinical need to identify biomarkers that predict and detect radiotherapy response in cancer. Using the unique capabilities of multi-scale photoacoustic imaging (PAI) for depicting tumour oxygenation and vasculature in vivo, we identified surrogate biomarkers of radiation response in two human breast cancer models (MCF7 and MDA-MB-231), comparing hypofractionated delivery with an ablative single dose scheme. Ex vivo immunohistochemistry results underpinned findings from mesoscopic and multispectral tomographic PAI, performed 24h pre-RT, 24h post-RT, and at endpoint. A denser and more mature vasculature of the MCF7 xenografts afforded an improved response to both RT schemes compared to MDA-MB-231, in terms of overall tumour oxygenation, tumour volume and proliferation. Increased intratumoural blood oxygen saturation and oxygen diffusion pre-RT were associated with improved outcomes and decreased proliferation, expected given the oxygen-enhancement effect in RT. In vivo PAI revealed the differential effect between ablative courses of RT in both models, with the ablative scheme altering the tumour vasculature as early as 24h post-RT, and pruning the looping vessels and total blood volume at endpoint in the more radiosensitive MCF-7 xenografts. An increase in blood oxygen saturation at endpoint was observed only in the MCF7 xenografts treated with hypofractionated RT, confirming the reduced oxygen consumption of damaged tumour cells, indicative of response. Thus, we showed that PAI could capture early RT response and inform on radioresistance, thus demonstrating promise of PAI as an in vivo and future clinical tool to monitor the tumour vascular response to RT.

cancer biology↗

bioRxiv2023

The in vitro dynamics of pseudo-vascular network formation.

Pseudo-vascular network formation capacity in vitro is considered a key characteristic of vasculogenic mimicry. While many cancer cell lines are known to form pseudo-vascular networks, little is known about the spatiotemporal dynamics of these formations. Here, we present a framework for monitoring and characterising the dynamic formation and dissolution of pseudo-vascular networks in vitro. The framework combines time-resolved optical microscopy with open-source image analysis for network feature extraction and statistical modelling. The framework is demonstrated by comparing diverse cancer cell lines associated with vasculogenic mimicry, then in detecting response to drug compounds proposed to affect formation of vasculogenic mimics. Dynamic datasets collected were analysed morphometrically and a descriptive statistical analysis model was developed in order to measure stability and dissimilarity characteristics of the pseudo-vascular networks formed. Melanoma cells formed the most stable pseudo-vascular networks and were selected to evaluate the response of their pseudo-vascular networks to treatment with axitinib, brucine and tivantinib. Our framework is shown to enable quantitative analysis of both the capacity for network formation, linked vasculogenic mimicry, as well as dynamic responses to treatment.

cancer biology↗

bioRxiv2023

The effects of skin tone on photoacoustic imaging and oximetry

SignificancePhotoacoustic imaging (PAI) provides contrast based on the concentration of optical absorbers in tissue, enabling the assessment of functional physiological parameters such as blood oxygen saturation (sO2). Recent evidence suggests that variation in melanin levels in the epidermis leads to measurement biases in optical technologies, which could potentially limit the application of these biomarkers in diverse populations. AimTo examine the effects of skin melanin pigmentation on photoacoustic imaging and oximetry. ApproachWe evaluated the effects of skin tone in PAI using a computational skin model, two-layer melanin-containing tissue-mimicking phantoms, and mice of a consistent genetic background with varying pigmentations. The computational skin model was validated by simulating the diffuse reflectance spectrum using the adding-doubling method, allowing us to assign our simulation parameters to approximate Fitzpatrick skin types. Monte Carlo simulations and acoustic simulations were run to obtain idealised photoacoustic images of our skin model. Photoacoustic images of the phantoms and mice were acquired using a commercial instrument. Reconstructed images were processed with linear spectral unmixing to estimate blood oxygenation. Linear unmixing results were compared with a learned unmixing approach based on gradient-boosted regression. ResultsOur computational skin model was consistent with representative literature for in vivo skin reflectance measurements. We observed consistent spectral colouring effects across all model systems, with an overestimation of sO2 and more image artefacts observed with increasing melanin concentration. The learned unmixing approach reduced the measurement bias, but predictions made at lower blood sO2 still suffered from a skin tone-dependent effect. ConclusionPAI demonstrates measurement bias, including an overestimation of blood sO2, in higher Fitzpatrick skin types. Future research should aim to characterise this effect in humans to ensure equitable application of the technology.

bioengineering↗