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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

Weideman focuses on misconceptions with regard to survival of Afrikaans
2006-05-19

From the left are Prof Magda Fourie (Vice-Rector: Academic Planning), Prof Gerhardt de Klerk (Dean: Faculty of the Humanities), George Weideman and Prof Bernard  Odendaal (acting head of the UFS  Department of Afrikaans and Dutch, German and French). 
Photo (Stephen Collett):

Weideman focuses on misconceptions with regard to survival of Afrikaans

On the survival of a language a persistent and widespread misconception exists that a “language will survive as long as people speak the language”. This argument ignores the higher functions of a language and leaves no room for the personal and historic meaning of a language, said the writer George Weideman.

He delivered the D.F. Malherbe Memorial Lecture organised by the Department Afrikaans at the University of the Free State (UFS). Dr. Weideman is a retired lecturer and now full-time writer. In his lecture on the writer’s role and responsibility with regard to language, he also focused on the language debate at the University of Stellenbosch (US).

He said the “as-long-as-it-is spoken” misconception ignores the characteristics and growth of literature and other cultural phenomena. Constitutional protection is also not a guarantee. It will not stop a language of being reduced to a colloquial language in which the non-standard form will be elevated to the norm. A language only grows when it standard form is enriched by non-standard forms; not when its standard form withers. The growth or deterioration of a language is seen in the growth or decline in its use in higher functions. The less functions a language has, the smaller its chance to survive.

He said Afrikaans speaking people are credulous and have misplaced trust. It shows in their uncritical attitude with regard to the shifts in university policies, university management and teaching practices. Afrikaners have this credulity perhaps because they were spoilt by white supremacy, or because the political liberation process did not free them from a naïve and slavish trust in government.

If we accept that a university is a kind of barometer for the position of a language, then the institutionalised second placing of Afrikaans at most tertiary institutions is not a good sign for the language, he said.

An additional problem is the multiplying effect with, for instance, education students. If there is no need for Afrikaans in schools, there will also be no  need for Afrikaans at universities, and visa versa.

The tolerance factor of Afrikaans speaking people is for some reasons remarkably high with regard to other languages – and more specifically English. With many Afrikaans speaking people in the post-apartheid era it can be ascribed to their guilt about Afrikaans. With some coloured and mostly black Afrikaans speaking people it can be ascribed to the continued rejection of Afrikaans because of its negative connotation with apartheid – even when Afrikaans is the home language of a large segment of the previously oppressed population.

He said no one disputes the fact that universities play a changing role in a transformed society. The principle of “friendliness” towards other languages does not apply the other way round. It is general knowledge that Afrikaans is, besides isiZulu and isiXhosa, the language most spoken by South Africans.

It is typical of an imperialistic approach that the campaigners for a language will be accused of emotional involvement, of sentimentality, of longing for bygone days, of an unwillingness to focus on the future, he said.

He said whoever ignores the emotional aspect of a language, knows nothing about a language. To ignore the emotional connection with a language, leads to another misconception: That the world will be a better place without conflict if the so-called “small languages” disappear because “nationalism” and “language nationalism” often move closely together. This is one of the main reasons why Afrikaans speaking people are still very passive with regard to the Anglicising process: They are not “immune” to the broad influence that promotes English.

It is left to those who use Afrikaans to fight for the language. This must not take place in isolation. Writers and publishers must find more ways to promote Afrikaans.

Some universities took the road to Anglicision: the US and University of Pretoria need to be referred to, while there is still a future for Afrikaans at the Northwest University and the UFS with its parallel-medium policies. Continued debate is necessary.

It is unpreventable that the protest over what is happening to Afrikaans and the broad Afrikaans speaking community must take on a stronger form, he said.

 

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