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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.

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Graduates convene with global leaders at the UFS 2015 Winter Graduation ceremonies
2015-07-07

Dr Hendrik Auret, dr Gerhard Bosman en dr Madelein Stoffberg.
Foto: Leonie Bolleurs

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The University of the Free State’s 2015 Winter Graduations, which took place from 1-2 July 2015 on the Bloemfontein Campus offered several highlights. Three global leaders received honorary doctorates. A further 2 000 degrees and diplomas were conferred to graduates in the seven faculties of the university.

For the first time in the history of the UFS, three PhDs in Architecture were awarded simultaneously. Hendrik Auret, Gerhard Bosman, and Madelein Stoffberg’s outstanding achievements are a milestone in the university’s pursuit of academic excellence.

Furthermore, three PhDs were conferred on graduates from the Department of Consumer Science in the Faculty of Natural and Agricultural Sciences. Ismari van der Merwe, Natasha Cronje, and Gloria Seiphetlheng set a precedent when they walked across the Callie Human stage to collect their doctorates at the same graduation ceremony.

This year, the university produced 66 Doctors of Philosophy in various fields of study. Six of these PhDs were awarded in the Department of Physics. Three graduates in the Department of Soil- and Crop- and Climate Sciences received PhDs at the Winter Graduation. They are Tesha Mardamootoo, Elmarie Kotzé, and David Chemei.

Dr John Samuel.
Photo: Johan Roux

Keynote speakers provide enlightenment to graduates

On Wednesday 1 July 2015, Dr John Samuel, SA’s leading education expert, addressed 707 diploma graduates from the Centre for Financial Planning Law and the School of Open Learning. For the graduates’ future reference, Samuel offered invaluable knowledge he had accumulated over the years as Chief Executive of the Nelson Mandela Foundation. “One of the lessons I have learnt was not only the importance of time, but it was in fact what being on time demonstrated,” he said. “Being on time was demonstrating respect, respect for the people you are meeting, and for the occasion.”

On the second day of graduation, Nataniël, South African singer, songwriter, and entertainer spoke to Master’s and doctoral graduates in the Faculties of Economic and Management Sciences, Humanities, Education, Health Sciences, Law, Theology, and Natural and Agricultural Sciences. His keynote spoke to the graduates’ sense of resolve in saying, “nothing is ever accidental. It is always with a purpose, it is your turn to make the world a better place.” He added that “it is important to strive for excellence and to be proud of what you are doing.”

Honorary doctorate recipients in a nutshell

Dr Samuel is one of the three exceptional global leaders to receive honorary doctorates from the university on 1 July 2015. His accolade was presented by the Faculty of Education. He has contributed to the Public Participation Education Network (PPEN) campaign as a founding member. He established the Centre for Education Policy Development, the Joint Working Group (for The National Party Government and the ANC), the National Education Conference, and the National Education and Training Forum. In addition, he made leadership contributions to the First Education and Training White Paper, the first Green Paper on Higher Education, and is the CEO of the Oprah Winfrey Leadership Academy for Girls. The WK Kellogg Foundation in the USA operates under his directorship.

Professor Heidi Hudson, Director of the Centre for Africa Studies at the UFS and Dr Lakhdar Brahimi.
Photo: Mike Rose from Mike Rose Photography

Dr Lakhdar Brahimi received an honorary doctorate from the Centre for Africa Studies. Algerian-born Brahimi was first involved with the United Nations (UN) in 1992, and has since been deployed all over the world on peacekeeping missions. Amongst many other countries, he has worked as a mediator for South Africa, Haiti, Afghanistan, Iraq, Syria, Democratic Republic of Congo, Cameroon, Burundi, Angola, Liberia, Nigeria, Sudan, and Côte d’Ivoire on behalf of the UN. He also played a direct role in South Africa’s democratic transition as a special representative in 1993/4.

Dr Mercy Amba Oduyoye received an honorary doctorate from the Faculty of Theology. Dr Oduyoye is widely regarded as one of the most influential women theologians in Africa. She was the first black woman to receive a degree in Theology in 1965 from Cambridge University in the United Kingdom. She continues to shift the paradigm of gender in theology internationally as the director of the Institute of African Women in Religion and Culture at the Trinity Theology Seminary in Ghana.

Dr Mercy Oduyoye.
Photo: Johan Roux

In closing the academic celebrations

Vice Rector: Academic, Dr Lis Lange, commended the class of 2014 for making their contribution to the educational system. Prof Jonathan Jansen, Vice Chancellor and Rector, also congratulated the graduates in closing.

“This is a day many have worked very hard towards, it is an enormous achievement as well as a development in the quality of research, and the courage to research,” he said in a vote of confidence.

Dr Khotso Mokhele, Chancellor of the UFS, applauded the university in light of the increased number of female graduates who completed their degrees with distinctions. The transcendence of demographics, both in terms of gender and race, on a postgraduate level, increases the hope of achieving gender equality in both the academic arena and South Africa.

More graduation news

A number of distinctions were also awarded during the two-day ceremony. For a list of these distinctions, follow this link.

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