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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

During 2011: Highlights at the UFS
2011-12-01

2011 was a phenomenal year in the life of the University of the Free State and the memorable moments will be engraved in the history of this proud institution.

World Universities Forum honours the UFS

The UFS was awarded the World Universities Forum (WUF) Award for Best Practice in Higher Education during 2010.The Best Practice Award recognises the most significant practices of the year around the world. The university’s implementation of a number of interlocking innovations to transform the institution is recognised with the award.

These innovations include: campus-wide racial integration for students; reinvigoration of the academic culture; nurturing of the most promising young scholars by means of the Vice-Chancellor's Prestige Young Scholars Programme; sending 71 first-year students to top American universities to assist with their development into non-racial campus leaders; the revision of the undergraduate curriculum to promote a cross-disciplinary approach to key societal problems; raising the entry requirements; the facilitation of open access to campus leadership through sessions with the Vice-Chancellor and Rector; extension of this spirit of dialogue internationally through the inauguration of its International Advisory Council consisting of key thinkers and practitioners; the identification of 20 of the most dysfunctional high schools in the Free State and the building of relationships with those schools.

This university-school partnership is based on a strict contract of reciprocal commitments to increase the chances of black children attending university. The WUF applauded this as the most innovative step.


New branding for our 107-year old institution

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Our university turned a fresh new page with the launch of a new brand that will take the institution on its path to new horizons.

Two primary brands were adopted – an evolved academic crest and a new marketing brand for the institution’s offerings and services. The very foundation of the UFS is built on a dynamic learning environment where academic excellence and the development of leadership qualities. The new brand seeks to adapt to the changing needs of society, without sacrificing its rich history and heritage.

The rebranding process involved one of the most expansive and intensive process of consultations with staff, alumni, Senate, Council and other stakeholders.

The new brand is anchored in the university’s renewed motto “In Veritate Sapientiae Lux” (In Truth is the Light of Wisdom), which has been evolved to embrace the diversity of the community at the university without losing its essence.


Archbishop Desmond Tutu receives an honorary doctorate

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One of the great sons of Africa, Archbishop Emeritus Desmond Tutu, received an honorary doctor of Theology and opened the International Institute for Studies in Race, Reconciliation and Social Justice on the Bloemfontein Campus at the beginning of 2011.

The Institute originated in the Reitz incident of 2008 and embodies the UFS’s determination to be a place where reconciliation, forgiveness and social justice would not only be studied, but where it would also be applied. Students and scholars from across the world can study the theory and practice of building societies across the boundaries of race, as well as religion, gender, disabilities and national origin.

By honouring Dr Tutu, the UFS recognises the contribution he has made in the field of Theology through his teachings and the books he has written. The UFS not only honoured him as a moral and religious leader who has maintained his integrity as a Christian, but also as “a great son of South Africa who has made a huge contribution to peace, reconciliation and justice in South Africa and in the world”.



Reconciliation closes book on the Reitz incident

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The Reitz incident, that has taken the UFS to front pages and news headlines, could come to closure this year with a reconciliation ceremony between the former students and staff members. The parties involved could meet in private and also took part in a public ceremony with many dignitaries witnessing the closure of the incident and repercussions it had.

Messages of apology were read by Prof. Teuns Verschoor, Vice-Rector: Institutional Affairs, on behalf of the UFS, and Mr Danie Grobler, on behalf of the former students. A message of acceptance of the apologies was read by Ms Emmah Koko on behalf of the workers.

Deputy Chairperson of the South Africa Human Rights Commission, Commissioner Pregs Govender, said of this historic event: “The courage and compassion shown by the workers together with the students’ willingness to embrace the spirit of change have enabled a process of justice, transformation and reconciliation that is an inspiring example for South Africa.”


Grade 12s attend first Leadership Summit

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More than 280 learners from all over South Africa and Namibia attended a three-day Leadership Summit on the Bloemfontein Campus in April 2011. The goal of the summit was to enable young leaders to develop their leadership capabilities by looking beyond their normal boundaries.

Prof. Jonathan Jansen, Vice-Chancellor and Rector, addressed the learners on leadership while Mr Louie de Necker, a training consultant, spoke about conflict resolution. Other highlights included a visit to the Boyden Observatory, picnic suppers, an introduction to residence life, a social evening, and a prize-giving ceremony aimed at learners who distinguished themselves as potential leaders during the three-day visit.


UFS honours great teachers

Our university and Sunday Times have joined hands in identifying 150 of the greatest teachers, who moved, inspired and transformed South Africans during their time at school. The project culminated in the book Great Teachers.

These are the teachers who stood out among their colleagues and made a lasting impact on their learners, inspiring them to excel, long after the mathematical equations and English literature tests are forgotten. The book is a powerful account of inspired and inspiring teachers.

All proceeds from the sales of the book will be used to provide bursaries to student teachers of today, who may become the great teachers for tomorrow’s generation.


Graduations now a celebration

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By changing its format, graduations are now a festival to celebrate years of hard work and dedication of students and lecturers at our university. Some of the changes include the gathering of the procession on the Red Square in front of the Main Building, from where it moves to the Callie Human Centre. The graduation programme is also filled with music and song items with various young speakers addressing and inspiring the audience.

A total of 83 doctorates were conferred this year, making it the highest number in the history of the university.


African Student Affairs Conference a huge success

The first African Student Affairs Conference (ASAC) was hosted by our university. The conference was attended by delegates from universities across the continent and was aimed to place the focus on issues relating to student affairs in an African context.

Delegates shared and exchanged strategies, ideas and resources, and discussed issues related to the work of student-affairs professionals. A delegate from Nigeria said it was an important conference for Africa and it should become a regular event.


Research published in Nature

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A research article on the work by a team under the leadership of Prof. Esta van Heerden, and counterparts in Belgium and the USA, has been published in the distinguished academic journal Nature on Thursday 2 June 2011.

The article – Nematoda from the terrestrial deep subsurface of South Africa – sheds more light on life in the form of a small worm (nematode) living under extreme conditions in deep, hot mines. It was discovered in one of the gold mines in the Free State.

The research can shed some new light on the possibility of life on other planets, previously considered impossible under extreme conditions. It also expands the possibilities into new areas where new organisms may be found.


Postgraduate School is one of a kind

Our Postgraduate School was launched with the aim of bringing research-bases education in line with national priorities and the focus of the UFS Academic Turnaround Strategy of 2010. It spans across our facilities.

The focus of the school is to produce graduates who are global citizens, research literate and able to reflect ethically on the purpose, process and product of research; to improve throughput rates of postgraduate students; and to make the experience of being a postgraduate at our university one which is stimulating, enjoyable and which contributes to the development of people beyond the limits of their disciplines.


Oprah Winfrey now a Kovsie

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World attention was drawn to our university when an honorary doctorate in Education was conferred on media icon Oprah Winfrey on 24 June 2011 at our Bloemfontein Campus. The graduation was probably the biggest ceremony of its kind in South Africa, with more than 4 500 people attending.

Our university honoured her for her accomplishments and unparalleled work as a global media leader, as well as a philanthropist with vision and foresight in the field of education and development.

Prof. Jonathan Jansen, Vice-Chancellor and Rector of our university, said: “It is a great privilege for us to be the first South African university to honour Ms Winfrey in this way and to be able to recognise a global icon of her stature.”


UFS doctors make history in South Africa

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Two procedures took the UFS to the forefront of the medical world this year.

History was made with the first implant of a special new aortic valve in South Africa. The advantage of this new valve is that it can be implanted percutaneously through a catheter from the groin. This eliminates the need for invasive surgery.

The valve is made from porcine pericardium (tissue derived from pigs) and is mounted on an expandable stent, which is threaded along an artery, until it reaches its desired position. The valve is especially useful in older patients who suffer from aortic valve disease and pose a high surgical risk. It also reduces hospitalisation time.

A rare malignant tumour was also removed in groundbreaking heart surgery. What makes this operation unique, is that the suspicious mass, identified in the heart of a 51-year old man, was rapidly growing into a highly invasive cardiac tumour seen in a small number of patients worldwide.

In the highly complex, 10-hour operation the entire right heart chamber had to be removed and the heart reconstructed.


School of Open Learning adds value

The activities of the new school are driven by a central principle: opening up access to those who have not had the opportunity to study at a higher-education institution due to geographical location, socio-economic circumstances or other factors.

Programmes are delivered through a blended-learning model, which blends contact teaching with distance education.

The school will collaborate with our various faculties, and is managing the continuing education-sponsored endeavours of the Faculty of Education. These include projects for in-service training of teachers in Mathematics, Natural and Physical Sciences, Languages, Literacy, Economic and Management Sciences, Technology and various areas of Management and Leadership.



Second group of young leaders abroad

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A second group of first-year students in the Leadership for Change Programme visited universities in the USA, Europe and Asia. Our university could extent the programme to 150 students, up from 71 in 2010.

These students are seen as a leadership core, not only for their university life, but also in public life outside the university borders.

The main purpose behind the programme is to expose students to positive models of racial integration. Their experiences will go a long way towards changing and enriching the minds of young leaders, who have committed to building a truly non-racial society in South Africa.


Odeion School of Music launched

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Our former Department of Music transformed into the Odeion School of Music. The name Odeion name portrays not only an excellent asset in the Free State, but also nationally and internationally.

The school’s new name bears the respected Odeion brand and a number of successful and respected ensembles operate under this brand. These include the residential Odeion String Quartet, student ensembles, the Junior Odeion String Quartet, the Odeion Sinfonia, and the Odeion Choir.

The formation of the school paths the way for more flexibility to complement its profile with new developments. These include the application of prestigious international experts as artistic fellows, membership to progressive European, jointly-developed degree programmes and curriculum development initiatives, the founding of a chair in Orchestra Conducting, a master’s degree in Arts Management, as well as the incorporation of bio-kinetics in the teaching methodologies of performance practice.


World-class Chemistry facilities opened

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World-class Chemistry facilities, with state-of-the art equipment, opened on the Bloemfontein Campus.

The upgrading of the facilities and addition and replacement of equipment were the single biggest investment at our university in a long time.

Specialised research by the Department of Chemistry includes X-ray crystallography, electrochemistry, synthesis of new molecules, the development of new methods to determine rare elements, water purification, as well as the measurement of energy and temperatures responsible for phase changes in molecules, the development of agents to detect cancer and other defects in the body, and many more.
 

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