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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

Bullying in schools: Everyone’s problem
2005-06-03

From left:  Prof Gerhardt de Klerk, Dean: Faculty of the Humanities; Prof Corene de Wet; Prof Rita Niemann, Head of the Department of Comparative Education and Educational Management in the School of Education and Prof Frederick Fourie, Rector and Vice-Chancellor of the UFS

It is not only learners who are the victums of bullying in schools, but also the teachers. Prof. Corene de Wet from the Department Comparative Education and Educational Management at the University of the Free State reported, against the background of two studies on bullying in Free State secondary schools, that bullying is a general phenomena in these schools.

Prof. de Wet, who delivered her inaugural lecture on Wednesday night, is from the Department Comparative Education and Educational Management which resorts under the School of Education at the University of the Free State. She is the first women who became a full professor the School of Education.

Prof. de Wet says, “A student is being bullied or victimized when he or she is exposed, repeatedly and over time, to negative action on the part of one or more students. Bullying always includes the intentional use of aggression, an unbalanced relationship of power between the bully and the victim, and the causing of physical pain and/or emotional misery.

In some Free State schools there are victims and perpetrators of direct and indirect verbal, as well as emotional, physical and sexual bullying.

“Adults who say that bullying are part of the growing-up process and parents who set not only academic expectations but also social expectations to their children cause that victims are unwilling to acknowledge that they are being bulled. Many parents are also unaware of the levels of bullying their children are exposed to.

“Some of the learners were at least once a month the victim of direct verbal harassment, 32,45% were assaulted by co-learners and 11,21% of them were at east once per week beat, kicked, pushed and hurt in any other physical way. Free State learners are very vulnerable to bullies at taxis and on the school yard they are mostly exposed to bullies in bathrooms.

“Learners are usually bullied by members of the same gender. However, racial composition also plays a role in some Free State schools. A grade 12 girl writes, ‘There are boys in my school who act means against black people. When the teacher is out they take a red pen and write on the projector and spray it with spirits. It looks like blood and they would say it is AIDS and my friends and I have it.’

“Educators must take note of bullying in schools and must not shrug it off as unimportant. Principals or educators could be find guilty of negligence. A large number of educator respondents, 88,29%, indicated that they would intervene in cases of verbal bullying and 89,71% would intervene if they saw learners being physically bullied. However, only 19,97% of the learners who were victims of bullying were helped by educators/ other adults from their respective schools.

“The learners’ lack of trust in their educators’ abilities and willingness to assist them in the fight against bullying has important implications for education institutions. The importance of training must be emphasised.

Learners bully their educators to undermine their confidence. In Prof. de Wet’s study on educator-targeted bullying in Free State schools 24,85% of the respondents were physically abused by their learners, 33,44% were the victims of indirect verbal bullying, and 18,1% were at one time or another sexually harassed by their learners. These learner offences may lead to suspension.

“Educators are not only victims of bullying; some of them are the bullies. The South African Council for Educators prohibits bullying by educators. It is worrying that 55,83% of the educators who participated in the research project verbally victimised learners, 50,31% physically assaulted learners and a small percentage was guilty of sexual harassment.

“Every educator and learner in South Africa has the right to life, equal protection and benefit of the law, of dignity, as well as of freedom and security of the person. These rights will only be realised in a bully-free school milieu.

“To oppose bullying a comprehensive anti-bullying programme, collective responsibility and the establishment of a caring culture at schools and in the community is necessary,” said Prof. de Wet.
 

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