Latest News Archive

Please select Category, Year, and then Month to display items
Previous Archive
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

Heart diseases a time bomb in Africa, says UFS expert
2010-05-17

 Prof. Francis Smit

There are a lot of cardiac problems in Africa. Sub-Saharan Africa is home to the largest population of rheumatic heart disease patients in the world and therefore hosts the largest rheumatic heart valve population in the world. They are more than one million, compared to 33 000 in the whole of the industrialised world, says Prof. Francis Smit, Head of the Department of Cardiothoracic Surgery at the Faculty of Health Sciences at the University of the Free State (UFS).

He delivered an inaugural lecture on the topic Cardiothoracic Surgery: Complex simplicity, or simple complexity?

“We are also sitting on a time bomb of ischemic heart disease with the WHO (World Health Organisation) estimating that CAD (coronary artery disease) will become the number-one killer in our region by 2020. HIV/Aids is expected to go down to number 7.”

Very little is done about it. There is neither a clear nor coordinated programme to address this expected epidemic and CAD is regarded as an expensive disease, confined to Caucasians in the industrialised world. “We are ignoring alarming statistics about incidences of adult obesity, diabetes and endemic hypertension in our black population and a rising incidence of coronary artery interventions and incidents in our indigenous population,” Prof. Smit says.

Outside South Africa – with 44 units – very few units (about seven) perform low volumes of basic cardiac surgery. The South African units at all academic institutions are under severe threat and about 70% of cardiac procedures are performed in the private sector.

He says the main challenge in Africa has become sustainability, which needs to be addressed through education. Cardiothoracic surgery must become part of everyday surgery in Africa through alternative education programmes. That will make this specialty relevant at all levels of healthcare and it must be involved in resource allocation to medicine in general and cardiothoracic surgery specifically.

The African surgeon should make the maximum impact at the lowest possible cost to as many people in a society as possible. “Our training in fields like intensive care and insight into pulmonology, gastroenterology and cardiology give us the possibility of expanding our roles in African medicine. We must also remember that we are trained physicians as well.

“Should people die or suffer tremendously while we can train a group of surgical specialists or retraining general surgeons to expand our impact on cardiothoracic disease in Africa using available technology maybe more creatively? We have made great progress in establishing an African School for Cardiothoracic Surgery.”

Prof. Smit also highlighted the role of the annual Hannes Meyer National Registrar Symposium that culminated in having an eight-strong international panel sponsored by the ICC of EACTS to present a scientific course as well as advanced surgical techniques in conjunction with the Hannes Meyer Symposium in 2010.

Prof. Smit says South Africa is fast becoming the driving force in cardiothoracic surgery in Africa. South Africa is the only country that has the knowledge, technology and skills base to act as the springboard for the development of cardiothoracic surgery in Africa.

South Africa, however, is experiencing its own problems. Mortality has doubled in the years from 1997 to 2005 and half the population in the Free State dies between 40 to 44 years of age.

“If we do not need health professionals to determine the quality and quantity of service delivery to the population and do not want to involve them in this process, we can get rid of them, but then the political leaders making that decision must accept responsibility for the clinical outcomes and life expectancies of their fellow citizens.

“We surely cannot expect to impose the same medical legal principles on professionals working in unsafe hospitals and who have complained and made authorities aware of these conditions than upon those working in functional institutions. Either fixes the institutions or indemnifies medical personnel working in these conditions and defends the decision publicly.

“Why do I have to choose the three out of four patients that cannot have a lifesaving operation and will have to die on their own while the system pretends to deliver treatment to all?”

Prof. Smit says developing a service package with guidelines in the public domain will go a long way towards addressing this issue. It is also about time that we have to admit that things are simply not the same. Standards are deteriorating and training outcomes are or will be affected.

The people who make decisions that affect healthcare service delivery and outcomes, the quality of training platforms and research, in a word, the future of South African medicine, firstly need rules and boundaries. He also suggested that maybe the government should develop health policy in the public domain and then outsource healthcare delivery to people who can actually deliver including thousands of experts employed but ignored by the State at present.

“It is time that we all have to accept our responsibilities at all levels… and act decisively on matters that will determine the quality and quantity of medical care for this and future generations in South Africa and Africa. Time is running out,” Prof. Smit says.
 

We use cookies to make interactions with our websites and services easy and meaningful. To better understand how they are used, read more about the UFS cookie policy. By continuing to use this site you are giving us your consent to do this.

Accept