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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

New multi-purpose residences open in January 2015
2014-06-18

The UFS is currently busy with exciting new accommodation developments on both the Bloemfontein and Qwaqwa Campuses.

This includes a new residence with a hotel and a conference/lecture hall on the western part of the Bloemfontein Campus and the building of another residence on the Qwaqwa Campus.

“We have done what was possible in our quest to maximise the number of beds available in the older residences on the Bloemfontein Campus,” says Quintin Koetaan, Senior Director: Housing and Residence Affairs at the UFS. “This we achieved by converting underutilised and unutilised dining halls and kitchens into bedrooms, which was totally insufficient to address the dire need for beds.”

“The new residence building will have different types of accommodation. I am very excited and look forward to the completion of this project. And this particular residence also brings a very exciting architectural design to the university environment.”

The residence, with multiple blocks for different accommodation, will be wheelchair friendly and numbering and signage will also be in braille. This futuristic-designed building will stand the test of time and will be provide student accommodation until 2030.The R60 million project is funded by the UFS and the Department of Higher Education and Training.

In step with international university accommodation trends – as with Yale's residential college system – this residence will house female first-years who will be mentored by postgraduate students. Postgraduates will be headhunted with the support of the Student Representative Council’s (SRC) postgraduate committee. These postgraduate students will represent all the faculties. Block A and B will accommodate 184 female first-years.

Each floor in this residence will have a study room, two lounges, a kitchen and a laundry for 25 students. Security will be very tight, with three levels of security: entrance to residence, corridor and individual bedroom door. There will also be perimeter camera surveillance and a security officer outside and inside the residence. 

 
Block C will accommodate postgraduate students. The ground floor will house eight single-bed roomed flats. The first floor will have 16 single rooms sharing a bathroom, kitchen and living room, as well as one double room with its own bathroom. The second floor will have 21 single rooms sharing a bathroom, kitchen and living room.

Block D will house 18 hotel-like en suites, with a dining room where breakfast will be served. The target market here will be visiting academics and other university-affiliated visitors. Prices will be competitive to those of local guesthouses and hotels.

Bookings have already opened. Guests will be able to book in and access the hotel desk 24/7. The dining room, accommodating up to 60 people, will not only be open for hotel guests, but also for postgraduate students and UFS staff. Bookings will therefore be essential.

The expansion of bed spaces also took place at the Qwaqwa Campus. In 2012 a 200-bed residence with a state of the art computer room was completed. As a follow-up to this development, another 248-bed residence is now being built. In this particular residence, there will be designated post-graduate accommodation for 48 students.

The project will be handed over at the end of October 2014, with the first intake planned for January 2015.

Another development at the Qwaqwa Campus is the Chancellor’s House Bed & Breakfast. This B&B, with its 5 en suite rooms, is open for business for all UFS staff.

 

For enquiries or bookings at this new accommodation facility, contact:

- Undergraduate (first-year ladies’ residence):
Monica Naidoo at +27(0)51 401 3455 or NaidooM@ufs.ac.za  

- Postgraduate:
Hein Badenhorst at +27(0)51 401 2602 or BadenH@ufs.ac.za  

- Hotel:
Ilze Nikolova at +27(0)51 401 9689 or NikolovaI@ufs.ac.za  

- Chancellor’s House Bed & Breakfast on Qwaqwa Campus:
Olga Molaudzi at +27(0)58 718 5030 or molaudziOD@qwa.ufs.ac.za

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