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04 December 2024 | Story André Damons | Photo André Damons
Breast Cancer Research 2024
The research team consist of Dr Beynon Abrahams (left), Viwe Fokazi, MMed.Sci student, and PhD student Songezo Vazi.

In an effort to better understand chemotherapeutic treatment response in triple negative breast cancer (TNBC) – known as an aggressive cancer with high recurrence and high mortality rate in breast cancer patients – researchers from the University of the Free State (UFS) developed a drug-resistant TNBC spheroid model that is physiologically more accurate in displaying the complexities involved in drug-resistance development.

Dr Beynon Abrahams, Lecturer in the Department of Basic Medical Sciences within the UFS Faculty of Health Sciences, says breast cancer remains the most frequently diagnosed cancer in women. It is also the most debilitating type of cancer responsible for the highest cancer mortality rates in women. Though various subtypes of breast cancer exist, TNBC is one that is of particular interest to his research team.

“TNBC is one of the most difficult cancer types to treat, due to lack of treatment targets. This often leads to treatment failure in TNBC patients, with drug resistance being a common occurrence, contributing to high death rates. TNBC is classified based on its lack of expression of common receptors such as the estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2, which are commonly expressed in other cancer subtypes.

“Characteristically, TNBC is known as an aggressive cancer with high metastatic potential (spreading of cancer), resulting in a poor prognosis for these patients. The current prescribed therapies for TNBC, entails multidrug combination systemic therapy including chemotherapeutic agents such as doxorubicin and cisplatin as adjuvant therapy. However, despite these therapeutic interventions, drug resistance is a common occurrence,” says Dr Abrahams.

The best available preclinical cell-based models should be used

For effective drug treatments to be developed for TNBC therapeutics, he continues, the best available disease models should be used to not only improve our understanding of the disease physiology and its numerous mechanisms involved in chemotherapeutic resistance development but also to provide accurate results when determining how safe and effective newly developed drugs are, before they may be considered for further development and testing on humans.

According to him, in preclinical cancer research the conventional methods employed to study disease mechanisms, drug action and drug resistance is ineffective. Firstly, the traditionally used preclinical 2-dimensional (2-D) cell culture models do not accurately recapitulate the architectural biology observed in vivo, second, the drug responses assessed in these models may provide inaccurate results and limit its translational potential, explains Dr Abrahams. Thus, more advanced cell-based models such as 3-dimensional (3-D) spheroids and organoids to name a few, should be considered as alternatives.

The UFS research team, in collaboration with the Centre of Excellence for Pharmaceutical Sciences (Pharmacen™) at the North-West University (NWU), recently took the undertaking to establish two triple negative breast cancer 3-D spheroid models, using the clinostat rotating bioreactor ClinoStar™ system, designed by CelVivo in Denmark. The project is funded by the National Research Foundation.

The ClinoStar™ system promotes the self-aggregation of single cells, and natural formation of 3-D spheroids, through slow rotation within a cell growth chamber known as an incubator. There are various techniques and methods available to develop spheroids and organoids, however the ClinoStar™ systems allow for the development of metabolically stable spheroids, over a longer period of time, as opposed to other methods. It also eliminates the sheer-stress conditions that are normally encountered when using 2-D cell culture models.

“We successfully established one chemotherapeutic-sensitive triple negative breast cancer spheroid model and one novel cisplatin-resistant triple negative breast cancer spheroid model. The chemo-sensitive TNBC spheroid model was evaluated for responsiveness against two clinically used chemotherapeutic agents, doxorubicin and cisplatin. We suggest that this model may be useful to screen novel compounds including traditionally used phytomedicinal material for anticancer activity.

“In our second model, the cisplatin-resistant TNBC spheroid model was also exposed to cisplatin and doxorubicin and demonstrated a resistant response in terms of growth and viability. We believe that this model may be useful to further explore drug resistance mechanisms and may also be used as a tool to assess the drug reversal potential of novel compounds. The value and impact of these models lies in that they may offer predictive drug responses that are closer to that observed in in vivo (animals), as opposed to 2-D cell cultures. This however needs to be assessed. We are currently in the process to fully characterise these spheroids models.”

Aim of the research

Dr Abrahams explains their research aims to merge the gap between conventionally used 2-D cell models and in vivo models, by providing a model that is physiologically more accurate in mimicking the in vivo conditions and complex pathways associated with drug resistance, which is otherwise not observed or accurately expressed in 2D models. “Although our research is preclinical and considered fundamental basic research, the translational potential of our spheroid models may provide options for exploring and testing alternative drugs that may be considered for translational research,” Dr Abrahams says.

Characterising other advanced cell-based cancer models

The team is currently in the process of further characterising the TNBC spheroid model based on protein and genetic expression profiles to elucidate potential therapeutic biomarkers for drug treatment as well as screening various phytomedicinal plants, to assess their antiproliferative and drug-resistance reversal potential. In addition, the researchers recently commenced a new research project that aims to develop a drug-resistant prostate cancer spheroid model using the Clinostar™ system with their collaborators at the NWU.

Advanced cell-based model research is still relatively ‘new’ in South Africa and Africa, compared to the global North. As a result, says Dr Abrahams, their NWU collaborators together with other stakeholders, initiated the establishment of the Society for Advanced Cell Culture Modelling for Africa (SACCMA) in 2021, which aims to develop the fields of advanced cell modelling, three-dimensional (3D) cell cultures, 3D bioprinting and stem cell research, in Africa. Our current inter-departmental  collaboration include researchers from the Pharmacology department, but we hope to build and expand our collaboration network in the near future.

News Archive

Eye tracker device a first in Africa
2013-07-31

 

 31 July 2013

Keeping an eye on empowerment

"If we can see what you see, we can think what you think."

Eye-tracking used to be one of those fabulous science-fiction inventions, along with Superman-like bionic ability. Could you really use the movement of your eyes to read people's minds? Or drive your car? Or transfix your enemy with a laser-beam?

Well, actually, yes, you can (apart, perhaps, from the laser beam… ). An eye tracker is not something from science fiction; it actually exists, and is widely used around the world for a number of purposes.

Simply put, an eye tracker is a device for measuring eye positions and eye movement. Its most obvious use is in marketing, to find out what people are looking at (when they see an advertisement, for instance, or when they are wandering along a supermarket aisle). The eye tracker measures where people look first, what attracts their attention, and what they look at the longest. It is used extensively in developed countries to predict consumer behaviour, based on what – literally – catches the eye.

On a more serious level, psychologists, therapists and educators can also use this device for a number of applications, such as analysis and education. And – most excitingly – eye tracking can be used by disabled people to use a computer and thereby operate a number of devices and machines. Impaired or disabled people can use eye tracking to get a whole new lease on life.

In South Africa and other developing countries, however, eye tracking is not widely used. Even though off-the-shelf webcams and open-source software can be obtained extremely cheaply, they are complex to use and the quality cannot be guaranteed. Specialist high-quality eye-tracking devices have to be imported, and they are extremely expensive – or rather – they used to be. Not anymore.

The Department of Computer Science and Informatics (CSI) at the University of the Free State has succeeded in developing a high-quality eye tracker at a fraction of the cost of the imported devices. Along with the hardware, the department has also developed specialised software for a number of applications. These would be useful for graphic designers, marketers, analysts, cognitive psychologists, language specialists, ophthalmologists, radiographers, occupational and speech therapists, and people with disabilities. In the not-too-distant future, even fleet owners and drivers would be able to use this technology.

"The research team at CSI has many years of eye-tracking experience," says team leader Prof Pieter Blignaut, "both with the technical aspect as well as the practical aspect. We also provide a multi-dimensional service to clients that includes the equipment, training and support. We even provide feedback to users.

"We have a basic desktop model available that can be used for research, and can be adapted so that people can interact with a computer. It will be possible in future to design a device that would be able to operate a wheelchair. We are working on a model incorporated into a pair of glasses which will provide gaze analysis for people in their natural surroundings, for instance when driving a vehicle.

"Up till now, the imported models have been too expensive," he continues. "But with our system, the technology is now within reach for anyone who needs it. This could lead to economic expansion and job creation."

The University of the Free State is the first manufacturer of eye-tracking devices in Africa, and Blignaut hopes that the project will contribute to nation-building and empowerment.

"The biggest advantage is that we now have a local manufacturer providing a quality product with local training and support."

In an eye-tracking device, a tiny infra-red light shines on the eye and causes a reflection which is picked up by a high-resolution camera. Every eye movement causes a change in the reflection, which is then mapped. Infra-red light is not harmful to the eye and is not even noticed. Eye movement is then completely natural.

Based on eye movements, a researcher can study cognitive patterns, driver behaviour, attention spans, even thinking patterns. A disabled person could use their eye-movements to interact with a computer, with future technology (still in development) that would enable that computer to control a wheelchair or operate machinery.

The UFS recently initiated the foundation of an eye-tracking interest group for South Africa (ETSA) and sponsor a biennial-eye tracking conference. Their website can be found at www.eyetrackingsa.co.za.

“Eye tracking is an amazing tool for empowerment and development in Africa, “ says Blignaut, “but it is not used as much as it should be, because it is seen as too expensive. We are trying to bring this technology within the reach of anyone and everyone who needs it.”

Issued by: Lacea Loader
Director: Strategic Communication

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